Investigating Esophageal Reflux With the Intraluminal Impedance Technique

Various methods for using epigastric (1) and intraluminal (2,3) impedance to describe gastroesophageal motility have been reported, but have not been established as standard clinical diagnostic procedures. The aim of this article is to illustrate a new application of impedance monitoring and to review the current literature, evaluating the potential and limitations of this technique with special emphasis on the pediatric patient. MULTIPLE INTRALUMINAL ELECTRICAL IMPEDANCE MEASUREMENT Theoretical Approach—In Vitro and In Vivo Evaluations In the late 1980s, a new procedure for evaluating the movement of fluids in the lumen of the gastrointestinal tract was developed at the Helmholtz-Institut für Biomedizinische Technik, Aachen, Germany (4,5): the multiple intraluminal electrical impedance measurement (IMP). Electrical impedance is defined as the ratio between voltage and current. It is measured in ohms and is, similar to resistance, inversely proportional to electrical conductivity. The basic principle of the new IMP technique is to record the changes in electrical impedance in the gastrointestinal lumen caused by the passage of a bolus (4). For measuring IMP, metallic, radiopaque, cylindrical electrodes are attached at defined distances to a catheter that is placed inside the gastrointestinal lumen (Fig. 1). For signal processing and recording, the electrodes are connected to impedance-voltage transducers and to a recording device outside the body by thin wires that run inside the plastic catheter. Impedance is measured bipolarly between paired electrodes (4), with two electrodes representing one measuring segment, that is, one “impedance channel” (Fig. 1). Each impedance channel represents one segment of defined length, and the total length evaluated is a function of the number of electrodes and the distance between them.FIG. 1.: Principle of the intraluminal impedance technique. Transsectional view of a luminal organ with surrounding body, organ wall, intraluminal impedance catheter, air, and bolus (= volume conductor). Direction of bolus movement depicted by bold arrow. Air is situated in front of the bolus. Impedance (Z) is measured bipolarly between each two neighboring electrodes placed on the catheter, resembling a measuring segment (impedance channel, Zn). Predefined electrode distance (x) and number of impedance channels (n). Extracorporal signal processing via impedance-voltage transducer connected with each impedance channel (dotted line). Online and offline evaluation and analysis with a display and recording device.The following principles are applied. The electrical conductivity of air is almost zero. The conductivity of a bolus (e.g., saliva, food, gastroduodenal contents) is relatively high, and the conductivity of the muscular wall is intermediate between the two (4,5). All components (air, bolus, organ wall, body) form a volume conductor around the catheter and the impedance electrodes (Fig. 1). The impedance between two electrodes, that is, one impedance channel, changes characteristically depending on the electrical conductance of the material surrounding the electrodes and depending on the phase of the contraction wave. Impedance decreases during the passage of a bolus with high conductivity, such as saliva, food, or gastrointestinal secretions, and increases during phases of lower conductivity, such as during the passage of air or during muscular organ wall contractions (Fig. 2). Impedance signals can be displayed online and also recorded digitally for subsequent offline analysis and printout. With high-resolution recordings (50- to 100-Hz sampling rate) in the esophagus, it is possible to distinguish among the resting state, bolus transit, and contraction of the muscular wall in each impedance tracing (6) (Fig. 2). In the resting state (phase 1), the impedance baseline is created by the relaxed muscular organ wall with its low electrical conductivity applied loosely to the measuring electrodes (Fig. 2). The temporary increase in impedance before passage of the bolus represents a small amount of air propelled in front of the bolus (phase 2). A sharp decrease in impedance follows as the fluid bolus enters the measuring segment (phase 3), and a subsequent increase in impedance occurs reflecting the exit of the bolus and the contraction of the esophageal wall after the bolus has passed the measuring segment (phase 4). Finally, the wall musculature relaxes and impedance returns to the resting state (phase 5).FIG. 2.: Schematic tracing of typical impedance changes during the passage of a bolus. Transsectional view of a luminal organ with surrounding body, organ wall, intraluminal impedance catheter, air, and bolus (= volume conductor). Direction of bolus movement depicted by bold arrow. Impedance (Z) is measured over time (t) between each two neighboring electrodes, resembling an impedance channel. The impedance value for each channel is displayed (•). The passage of a bolus is characteristically divided into five phases: phase 1, resting state, impedance of the relaxed muscular organ wall; phase 2, increase in impedance caused by air propelled in front of a bolus; phase 3, actual bolus passage, impedance of a bolus with high conductivity; phase 4, wall constriction, increase of impedance when bolus has passed; phase 5, wall relaxation, impedance returns to resting state (= impedance baseline).By using multiple impedance channels, arranged sequentially on a single catheter, the direction of bolus movement in any lumen and its muscular contractions can be determined (Fig. 3). All impedance channels are displayed and recorded simultaneously. A mobile computer system for data acquisition and software for visual analysis of IMP recordings have been developed (Helmholtz-Institut für Biomedizinische Technik, Aachen, Germany).FIG. 3.: Schematic tracing of a typical multichannel impedance recording during the passage of a bolus. Transsectional view of a luminal organ with organ wall, intraluminal impedance catheter, air, and bolus. Direction of bolus movement depicted by bold arrow. Impedance (Z) is measured over time (t) in each impedance channel. The impedance values of selected impedance channels 2 (Z2), 6 (Z6), and 10 (Z10) at the current bolus position are displayed (•). Typical sequential impedance changes attributable to the passage of a bolus appear first in Z10, then in Z6, and then in Z2, thus reflecting the direction of the bolus movement (shaded arrow). t1 = bolus passage (phase 3) through Z10, bolus entering into Z6, air entering (phase 2) into Z2; t2 = bolus exit from Z10, bolus passage (phase 3) through Z6, bolus entering into Z2; and t3 = return to resting state (phase 5) in Z10, impedance of contracted muscular wall (phase 4) in Z6, bolus exit from Z2.Impedance tracings of the esophagus are analyzed visually for the typical changes attributable to the passage of a bolus (Fig. 2). If these changes first appear in the most proximal impedance channel and proceed sequentially to the more distal channels, they are interpreted as antegrade bolus movement, that is, a swallow (6). If the impedance changes appear first in the distal channels and proceed sequentially to the more proximal channels, they are interpreted as retrograde bolus movement, that is, gastroesophageal reflux (GER). In Figure 3, assuming the luminal organ pictured is the esophagus in the upright position, the impedance tracing shows the typical sequential changes during a GER episode. Hereafter, the term gastroesophageal reflux is used only if this typical pattern of retrograde bolus movement is noted on IMP tracings. Preliminary studies performed in vitro have defined the measurements of different tissues, fluids, and soft foods (4). In these initial experiments, an eight-channel impedance catheter was used with a measuring current of less than 6 μA. This current was chosen because it is well below the stimulation threshold of human nerves and muscles and, therefore, does not complicate the impedance recordings with electrically stimulated motor activity (5). In a theoretical and experimental approach, the typical phases of bolus passage were verified. In vivo studies of the esophagi and small intestines of healthy volunteers have demonstrated conformity with the theoretical and in vitro defined phases, and therefore have demonstrated the potential applicability of the method for clinical use in humans. Figure 3 shows typical impedance changes during deglutition and contraction activity. Clinical Application in the Adult Esophagus Studies in healthy adults (6,7), during which fluoroscopy, manometry, and multiple-site impedance measurements of the esophagus were performed simultaneously, have helped to define standards for normal motor function during swallowing of food or fluid and to define standards for assessing GER and its esophageal clearance. In these studies, the temporal relation between the pressure tracings and the different IMP phases were analyzed (Fig. 4). In addition to confirming the typical qualitative changes in impedance, these combined measurements demonstrate a consistent association between manometric events and impedance changes (7). The passage of air and fluid bolus causes marked changes in impedance (phases 2 and 3) but only a slight increase in pressure. The maximum increase in pressure results from the contraction of the muscular organ wall as the bolus exits the organ segment (phase 4).FIG. 4.: Schematic tracing of typical impedance and pressure changes during the passage of a bolus. Transsectional view of a luminal organ with surrounding body, organ wall, intraluminal combined impedance, and manometry catheter, air, and bolus. Direction of bolus movement depicted by bold arrow. Impedance (Z) and pressure (P) are measured simultaneously over time (t). The passage of a bolus is divided into five phases (see Fig. 2). The air pushed forward by the bolus (phase 2) causes an increase in impedance and a small increase in pressure. The maximum increase in pressure (phase 4) results from the contraction of a segment of the muscular organ wall. The impedance baseline characterizes the impedance value of the resting state (phase 5). A: Return of the impedance value to baseline at the beginning of phase 3, indicating bolus entry into the impedance measuring segment. B: Lowest impedance value during phase 3, indicating maximal bolus conductivity within the measuring segment. C: Highest impedance value during phase 4, indicating maximal muscular wall contraction.From the defined electrode distance and the time difference between the appearance of the impedance patterns in sequential impedance channels, the velocity of the bolus passage and the physical length of the bolus in each segment can be calculated (4,7). With this technique, it is possible to analyze changes in bolus velocity and bolus length during passage through the esophagus. Because the manometric pressure maximum during a bolus passage is qualitatively mirrored in IMP phase 4, the velocity of a contraction wave also can be calculated from the multichannel impedance tracing. A difference between the velocity of the bolus passage (phase 3) and the velocity of the corresponding contraction wave (manometric pressure maximum and IMP phase 4) has been documented in the esophagus. This is important supplemental information to that obtainable with single-channel manometry. In the first clinical study using impedance measurements for the investigation of esophageal motility, adults with reflux esophagitis and healthy volunteers were investigated with IMP and manometry (8) (Fig. 4). Impedance patterns in the upper and lower esophagus after test meals were documented and compared. As described previously (4,7), bolus velocity was calculated from the distance between the impedance electrode pairs and the time elapsed between the appearance of the typical patterns in sequential impedance channels. A significant decrease of bolus velocity as the bolus moved distally in the esophagus was noted in all subjects. As expected, bolus velocity increased with decreasing viscosity of the test meal. Interestingly, patients with reflux had a marked delay of the bolus passage in the distal esophagus compared with controls. The impedance value in phase 5 (resting state) stayed above the baseline and decreased slowly only after a second swallow. This phenomenon could be demonstrated only in patients with reflux and was interpreted as slow relaxation over a prolonged period of time, possibly an important contributor to the pathogenesis of reflux esophagitis. Because this activity was not seen in the manometry tracings, it was thought to most likely be a nonoccluding contraction. This study (8) demonstrated the potential of IMP in investigating the physiology of esophageal motility and the pathophysiology of its disorders in selected patients. In light of these finding, characterization of esophageal bolus transport in healthy adults was studied with IMP (9). Time intervals between corresponding channels were calculated for the different IMP phases (Fig. 2), and pharyngogastric transit time of a bolus was determined. To study the dynamics of bolus transport, the velocity of different bolus parts (head, body, and tail) was calculated for the various anatomic segments (4,7). Three specific points were characterized (Fig. 4): the A point, which is the entry of the bolus head into a specific IMP segment and is indicated by return of the impedance value to baseline at the beginning of phase 3; the B point, which is the moment of maximal bolus conductivity in one IMP segment and is indicated by the lowest impedance value during phase 3; and the C point, which is the moment of maximum luminal occlusion associated with the muscular contraction that clears the bolus tail. The C point is indicated by the maximal impedance value during phase 4. In all subjects, highly reproducible impedance patterns related to the transport of a bolus were observed (9). Air was typically swallowed with and propelled ahead of the bolus. Bolus velocity, calculated from points A, B, and C in sequential channels, generally slowed down in the distal esophagus and accelerated in the upright position. The spatial and temporal relations of the complex process of bolus transit from the pharynx into the stomach have therefore been described in detail. In a subsequent study (10), IMP was used simultaneously with standard pH recording in adults with reflux esophagitis. Both catheters were passed transnasally into the esophagus and stomach. Impedance tracings were analyzed visually for the occurrence of GER, indicated by the typical impedance pattern showing retrograde flow (Fig. 3). In relation to overall reflux event detection by IMP, pH monitoring demonstrated a sensitivity of 71.6%, whereas the sensitivity of IMP compared to pH monitoring was 98.8% (10). This difference was mostly because of nonacid reflux episodes that were not detected by pH monitoring. Multiple intraluminal electrical impedance measurement was valuable in diagnosing GER independent of the pH of the refluxate. The simultaneous use of pH recording and IMP seemed to be a promising method for detecting acid and nonacid reflux. More recently, IMP has been used to measure gas and liquid reflux in the esophagi of healthy adult volunteers (11). With simultaneous IMP, manometry and pH recording it was found that gas reflux (IMP phase 2) was not necessarily the initial event during acid gastroesophageal reflux. These findings contrast with previous results (6,8,9) and must be verified by future investigations. However, their results (11) emphasize the value of IMP in detecting events in the esophagus other than those identified by pH probe alone. Further studies of adult patients with reflux disease and healthy controls using IMP and pH monitoring (12,13) have been aimed toward a more precise characterization of the postprandial refluxate. Most important, the applicability of a new portable impedance recording device (Helmholtz-Institut für Biomedizinische Technik, Aachen, Germany) has been demonstrated. Another center reported its findings using the same IMP technique (Multichannel Intraluminal Impedance; Sandhill Scientific, Englewood, CO, U.S.A.) to study esophageal bolus transport in healthy adults (14) and to investigate the effect of omeprazole on acid and nonacid reflux in adult patients with heartburn (15). These reports established the applicability of IMP in adult esophageal function testing and evaluated its role in nonacid reflux detection when symptoms persist after acid suppression. Clinical Applications in the Infant Esophagus Impedance monitoring seems to offer a number of important advantages in understanding and assessing GER in children. Because it is not pH dependent, IMP can identify all episodes of reflux that occur, many of which may be missed in standard pH probe assessment (10,11). The direction of bolus flow can be analyzed, adding to an understanding of the efficiency of acid clearance from the esophagus. By assessing the underlying motor function of the esophagus on a continuous basis, IMP may allow identification of individuals in whom reflux is primarily a function of esophageal motility and those in whom reflux is primarily a function of lower esophageal sphincter dysfunction. In the first pediatric study (16), IMP was used to investigate esophageal motility in infants with symptoms of reflux disease (17). A flexible, six-channel impedance catheter with an electrode spacing of 1.5 cm and an outer diameter of 1.5 mm (Helmholtz-Institut für Biomedizinische Technik, Aachen, Germany) was fitted with a distal pH sensor. This single, combined catheter was placed transnasally with a total IMP measuring length reaching from the hypopharynx to the cardia. As previously described in adults (6), the typical patterns of antegrade and retrograde bolus movements were identified in the esophageal impedance tracings of these infants (Fig. 5). Again, the term GER is used only if the typical pattern of bolus reflux was noted in IMP tracings. Gastroesophageal reflux episode distribution in relation to the previous feeding was recorded. The most proximal impedance channel that showed the typical changes during a GER episode was defined as the height reached by the refluxate in the esophagus. The pH of each GER episode was documented, and the differences between esophageal acidity and volume clearance were clearance was defined as the time to at of the initial baseline impedance which to a clearance of than of the volume in the measuring segment, as from in vitro studies (4). In acid reflux episodes acidity clearance was defined as the time to return the esophageal pH to a than tracing of retrograde esophageal bolus passage with sequential decrease of impedance (Z) over time (t) (impedance channel channel Z6, and a of pH 4, resembling an acid gastroesophageal reflux to impedance channel pH is situated at the of channel bolus passage from distal to these studies, most postprandial reflux episodes were not detected by pH monitoring because the pH of the refluxate was not less than (Fig. been by the of reflux episodes were not identified as reflux episodes by pH probe because the of pH less than was In relation to the overall reflux event detected by IMP, pH monitoring demonstrated a sensitivity of whereas the sensitivity of IMP was Most GER refluxate reached the proximal impedance channel situated in the hypopharynx (Fig. 5 and In almost all GER volume clearance was after a single swallow. events in infants during these studies, and the thin catheter seemed to be well The occurrence of nonacid GER in the postprandial period the IMP for GER detection in this Multiple intraluminal electrical impedance measurement also was a valuable for the physiology of reflux clearance and swallowing in tracing of retrograde esophageal bolus passage with sequential decrease of impedance (Z) over time (t) (impedance channel channel Z6, and pH 4, resembling a nonacid gastroesophageal reflux to impedance channel pH is situated at the of channel bolus passage from distal to IMP, studies have to the between reflux and in infants with symptoms have been investigated simultaneously with IMP, and were analyzed in this study for the typical IMP pattern of GER, and any temporal association with other recorded was As expected, most documented GER episodes were However, the most new information was the of a temporal association between GER episodes and (Fig. The height reached by the refluxate in the esophagus was identified as one of that a complex pattern the from to material a could be the of or episodes of during reflux A of an increase of with increased height reached by the a decreased during and the between GER and this However, a between GER and or is not and must be the aim of during an episode of may lower esophageal sphincter relaxation, therefore, or GER the use of pH monitoring seems to be for detecting GER associated with symptoms that used the impedance technique found different results the of in infants the IMP to be a and valuable diagnostic for this tracing of retrograde esophageal bolus passage with sequential decrease of impedance (Z) over time (t) (impedance channel channel Z6, and pH 4, resembling a nonacid gastroesophageal reflux to impedance channel association with body movement and flow and wall pH is situated at the of channel bolus passage from distal to studies that used simultaneous recording and IMP found a temporal between GER and body movement in infants Preliminary data from clinical investigating the for GER for of the physiology and pathophysiology of reflux clearance and the physiology of transit patterns are to increase the of pH probe analysis have the simultaneous use of IMP but the advantages of using the new technique are INTRALUMINAL IMPEDANCE intraluminal impedance measurements have new into the physiology and pathophysiology of gastrointestinal function in and disease of antegrade and retrograde bolus movement, length of the swallowed or bolus, and direction and velocity of bolus movement can be described (7). of GER can be characterized by their height in the esophagus and by their This is in the postprandial period and in clinical of pH monitoring and IMP of GER episodes intraluminal impedance measurement is also a valuable for the process of GER clearance and swallowing However, normal values in various pediatric to be With clinical use of IMP in data be IMP can be performed in studies with a that may as their controls. This be in studies of To association IMP can be into other diagnostic for manometry and studies recordings may demonstrate temporal that may be missed when acid reflux is measured because of the highly procedure of and visually evaluating the tracings, IMP is a For clinical use of IMP, software to in detecting patterns and in must be developed and studies of visual analysis to clinical between and is in this is toward a portable recording device for impedance studies in all in IMP technique of to describe bolus bolus and bolus and lumen at any point the intraluminal measuring catheter. are to impedance values into the analysis of the tracings of catheter allow to any clinical or luminal The of impedance recordings is only by the of the intraluminal impedance measurement has been used in the of adults to investigate the physiology and pathophysiology of transport of the technique in the or tract be data is in at this events or of impedance measurements have not been reported, and IMP studies are well by infants and children. However, IMP or but the of assessment of esophageal and gastrointestinal motility is for pediatric patients. studies and the technique and understanding of esophageal motility, its and associated The and for their continuous