Gastroenterology Service, Cleveland Clinic Foundation, Cleveland, Ohio 44195
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ABSTRACT |
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Multichannel intraluminal impedance (MII) is a new diagnostic test for gastroesophageal reflux disease (GERD). The objective of this report is to determine the accuracy of MII in detecting individual reflux events (REs) identified by pH probe and manometry, as well as their clearing in patients with severe GERD compared with normal volunteers. Ten severe GERD patients and 10 normal volunteers underwent simultaneous manometry [7 sites: gastric, lower esophageal sphincter, esophagus (4), pharynx], pH, and MII (6 sites in esophagus) for 15 min in the left and right recumbent posture while fasting. We found that patients had 30-fold more REs than normal volunteers (41 ± 11 vs. 1.3 ± 0.4), and 95% of all REs were detected by MII. An average 15-fold fall in impedance with liquid and fivefold rise with gas made REs and their composition easy to detect with MII. In the right recumbent posture, nearly all REs detected by MII were liquid (98%, 98/100). In contrast, all 283 REs detected by MII in the left recumbent posture were gas. Nearly all REs detected by MII were cleared (98%, 368/374). Mean acid clearing time was threefold longer (47 s) than clearing time by either manometry (15 s) or MII (13 s), primarily due to acid rereflux, i.e., additional acid REs during acid clearing. We conclude that MII is accurate in detecting REs identified by manometry and/or pH probe, their composition, and their clearing.
pH monitoring; common cavities; gastroesophageal reflux disease
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INTRODUCTION |
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MULTICHANNEL INTRALUMINAL impedance (MII) is a new method for gastroesophageal reflux disease (GERD) patients that assesses transit based on changes in resistance to current flow between adjacent electrodes when a bolus passes between them (2). MII detects gastroesophageal reflux events (REs) when aboral flow occurs across two or more distal electrodes in the esophagus, and MII can also assess whether the composition of the refluxed gastric contents is gas, liquid, or mixed.
Three recent reports (6, 7, 9) examined the promising role of MII combined with pH in detecting acid and nonacid REs. Two reports compared GERD patients with normals, one utilizing postprandial simultaneous manometry, pH, and MII in the upright posture, and the other ambulatory 24-h MII-pH. Both reports found that total REs were similar in normals and GERD patients, although acid REs made up a greater proportion of REs in GERD patients. In addition, mixed REs were more common than liquid-only REs (6, 7). In another report of combined MII-pH after a refluxogenic meal in GERD patients, omeprazole decreased acid REs; however, total REs were unchanged, because nonacid REs increased (9). In these reports, mean RE frequency was 10.5/hr (6) and 10/hr (9) in the short-term studies but only 46 per 24 h in the 24-h study (7).
Present reflux tests have fundamental differences in the measurement parameter analyzed. The pH probe measures acid concentration in a volume of unknown amount. Thus when gastric contents with a pH of 2 refluxes into the esophagus, a gallon of refluxant with pH 2 looks the same to the pH probe as an ounce of refluxant with pH 2. Conversely, the common cavity (detected by manometry) can't assess concentration of any chemical component, especially acid. Instead, the common cavity detects when enough volume of gastric contents enters the esophagus to raise intraesophageal pressure to that of intragastric pressure. However, that threshold volume and the final refluxed volume is unknown. Measurement characteristics of REs detected by impedance are unknown.
The purpose of this report is fourfold: 1) to validate the accuracy of MII in detecting individual REs in the most challenging situation, which is maximizing RE frequency by studying only patients with severe GERD and maximizing RE detection by combining manometry and pH monitoring; 2) to compare clearing of REs by pH, MII, and manometry; 3) to compare refluxant composition in different postures; and 4) to assess the measurement characteristics of impedance.
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MATERIALS AND METHODS |
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Study Population
Ten symptomatic patients (age 53 ± 4; 5 males, 5 females) with severe GERD were selected on the basis of two criteria: 1) moderate or severe GERD by endoscopy [thin erosions (n = 4); confluent ulcerations (n = 2); long-segment Barrett's esophagus (n = 4)]; and 2)Study Design
All subjects underwent simultaneous manometry, pH, and MII in the fasting left and right recumbent postures. Some severe GERD patients were also monitored after a nonrefluxogenic meal. Subjects were studied in accordance with protocol 3565, which was approved by the Institutional Review Board of the Cleveland Clinic Foundation on March 15, 2000. Written informed consent was obtained.Simultaneous esophageal manometry, MII, and pH monitoring.
A multichannel esophageal manometry catheter with a 7-cm distal sleeve
(DentSleeve) was passed through the nose and into the esophagus so that
it straddled the lower esophageal sphincter (LES). A 2.13-mm MII-pH
catheter (model Z-TC; Sandhill) was passed adjacent to the manometry
catheter such that the perfused side ports and MII sites had the
configuration shown in Fig. 1. Swallows were recorded by an air-perfused hypopharyngeal port. All data were
recorded simultaneously by the Sandhill Insight data-acquisition system
for subsequent analysis.
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Definition of REs and clearing.
The pH probe defined a RE traditionally (pH-RE); i.e., a fall in pH
from >4 to <4, and acid clearing time (ACT) of seconds until pH 4 was
again achieved. Manometry defined a RE as when a common cavity
occurred. A common cavity was defined as an increase in intraesophageal
pressure from gastroesophageal pressure equilibration that was not
associated with increased intraesophageal pressure from a swallow,
dysmotility, or movement. Its duration was seconds until the
peristaltic contraction decreased intraesophageal pressure to baseline.
Acid rereflux was defined as a common cavity while pH was already <4,
i.e., rereflux of acidified gastric contents into the esophagus before
successful acid clearing after a traditional pH-RE (Figs.
2, 3, and 4).
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Statistical analysis. Descriptive data are presented as means ± SE. Comparative data were by Mann-Whitney rank-sum test and Wilcoxon's signed-rank test.
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RESULTS |
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MII Detection of Acid and Nonacid REs in Patients and Normal Volunteers
Patients had 30-fold more REs detected by the pH probe and/or manometry than normal volunteers (41 ± 11 vs. 1.3 ± 0.4; P < 0.001), and MII detected 95% of all REs. Because REs were uncommon in normal volunteers, only data from patients are subsequently presented (see Table 1).
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Most traditional acid REs (77%) and nearly all acid rereflux events (92%) were detected by MII. Most acid rereflux REs were undetectable by the pH probe even when using expanded pH criteria of a further pH fall >1 unit while pH was <4, because 72% had a pH fall <1 unit. As expected, most of the traditional acid REs (77%, 33/43) and nearly all acid rereflux events (98%, 56/57) were liquid rather than gas determined by MII. Only one RE was of mixed composition, i.e., a gas RE followed <3 s later by a liquid RE.
Nonacid REs were 2.4-fold (289:119) more common than acid REs, and 99% were detected by MII. The vast majority (96%, 275/285) of nonacid REs detected by MII contained only gas.
Characteristics of Liquid and Gas REs Detected by MII
The magnitude of impedance fall with liquid and rise with gas was typically dramatic, making REs detected by MII easy to detect. The average fall in impedance due to liquid reflux with traditional acid REs (740 ± 150 to 45The average rise in impedance due to gas reflux was fivefold
(1,657 ± 100 to 8,475 ± 160 ; Fig. 4). During the course
of all studies, an impedance value >7,000 was unusual except in the presence of gas in the esophagus. Nonacid liquid reflux was too infrequent for meaningful characterization.
The proximal extent of aboral liquid or gas flow could be determined by MII. Only 33% (33/99) of fasting liquid REs reached either of the two proximal sites despite being in the recumbent posture. However, 63% (179/286) of fasting gas REs reached a proximal site.
Comparison of Left vs. Right Recumbent Posture on Fasting RE Frequency and Composition
REs detected by pH probe and/or manometry were 2.5-fold (286:122; P < .01) more common in the left recumbent posture than the right. Of individual patients, 9 of 10 patients had
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In the right recumbent posture, 83% (101/122) of REs detected by pH and/or manometry were detected by MII, and 98% (99/101) of these REs were characterized by MII as liquid (Figs. 2 and 4).
In the left recumbent posture, 99% (283/286) detected by pH and/or manometry were detected by MII. All left recumbent REs detected by MII were characterized as gas only (Figs. 3 and 4). Only 3% (8/283) of these gas-only REs were associated with a fall in pH to <4.
Clearing of REs
Nearly all REs detected by MII were cleared (98%, 368/374). Acid REs and common cavities were cleared by definition. Acid clearance time was longer (47 ± 16 s; n = 45; P < 0.01) than clearance time by MII or manometry (15 ± 2 and 13 ± 1 s, respectively) in REs detected concurrently as a traditional acid RE and a RE by MII and/or manometry. However, clearing of the traditional acid REs occurred in two very different patterns. In the first pattern, traditional acid REs were not interrupted by acid rereflux and cleared in a similar amount of time to either MII or manometry. In contrast, 38% (17/45) of traditional acid REs had clearing interrupted by acid rereflux, resulting in their mean ACT being sevenfold longer (101 ± 40 s; P < 0.001). An average of four acid rereflux events (range 1-28) occurred during clearing of these traditional acid REs, resulting in the prolonged ACT (Table 3 and Fig. 2).
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Clearing time by MII was very similar to manometry in either an acid or nonacid environment in REs detected by both methods. Qualitatively, the magnitude of impedance change made clearing easier to detect by MII, which typically showed a small overshoot (Fig. 4). As Figs. 2 and 3 show, liquid or gas reflux by MII was completely cleared before the primary or secondary esophageal peristaltic contraction that followed each common cavity.
Postprandial (Nonrefluxogenic Meal) Reflux, Right Recumbent Posture
All six patients with fewer than five REs in the right recumbent posture had liquid REs after the nonrefluxogenic meal. The mean was 8.3 ± 2, and range 1-14. All MII characteristics were similar to fasting liquid REs, except that more reached a proximal esophageal site (58%, 34/59) (Fig. 5). ![]() |
DISCUSSION |
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A primary goal of this study was to determine whether MII was capable of distinguishing frequent individual REs occurring close together. The challenge was great, because our gold standard (RE detected by either or both manometry and pH) detected a mean frequency of 41 REs per 30 min, 5-fold more than the frequency of previous reports (6, 7). This goal was achieved because 95% were detected by MII.
Another goal was to compare clearing by the three methods, once a RE was detected. Clearing of REs by pH was slower than either manometry or MII, which were nearly identical in duration. This was for two reasons. First, acid clearing is a two-step process: 1) rapid volume clearing of nearly all of the bolus and 2) slow neutralization by saliva of the acidified residual (1). Neither manometry nor impedance were sufficiently sensitive to detect the small acid residue in the second step of acid clearing. Second, and more important, our report found that additional acid REs detected by MII or manometry during acid clearing (or acid rereflux) commonly aborted acid clearing attempts after traditional acid REs, often repeatedly, before acid clearance was finally achieved. This supports and extends our previous reports on the role of acid rereflux in patients with severe GERD. First, simultaneous manometry, pH, and scintigraphy found that 67% of acid REs in patients with severe esophagitis postprandial were acid rereflux rather than traditional acid REs (4), and our present study extends these findings to the fasting interval. Second, we found that acid rereflux after a traditional acid RE is the most common cause of prolonged daytime traditional acid REs in severe GERD patients, rather than decreased peristaltic amplitude or decreased swallowing rates (5).
The dramatic effect of posture on RE composition confirms and extends
our previous report (3). In that study, fasting patients with severe GERD had recurring common cavities with a pH >4 in the
left recumbent posture, which we assumed to be gas in the absence of a
method to confirm gas-only reflux. MII confirms that fasting REs in the
left recumbent posture are nearly always composed only of gas. Our
previous report also found primarily acid reflux by pH probe in the
right recumbent posture (3), and MII confirms nearly all
REs in the right recumbent posture are liquid only. We (3)
previously studied the effect of posture on RE composition by barium
ingestion in different postures (Fig.
6), and showed that refluxant composition
is a result of the EG junction's location relative to the
stomach's air-fluid interface. In the left recumbent posture, liquid
gastric contents (or barium) lie in the dependent body of the stomach,
and only gas is available at the EG junction for reflux into the
esophagus. This recurring gas-only reflux is profoundly abnormal,
because gas reflux is suppressed in recumbent normal individuals
(10). However, it is not pathophysiologically important,
because it contains no damaging component. In contrast, the right
lateral posture places the EG junction in a dependent position where
liquid gastric contents (or barium) collect above or near a submerged
EG junction. Thus acidified liquid gastric contents are present at the
EG junction and are available for reflux.
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MIIs measurement characteristics are more similar to the common cavity than the pH probe. MII identified nearly all nonacid and acid rereflux REs detected by the common cavity and not by the pH probe. Furthermore, clearing times by MII and manometry (common cavity) were nearly identical in acid, nonacid, gas, or liquid environments, and shorter than in acid clearing.
In our opinion, qualitative and technical advantages favor MII rather than the common cavity as a complementary test to the pH probe in GERD patients. First, the magnitude of impedance change with MII allowed REs to be more easily detected than the intraesophageal pressure increase in a common cavity and also made RE clearing more easily assessed than intraesophageal pressure fall at the end of a common cavity. Second, MII is not affected by events that increase intraesophageal pressure, such as movement or talking. Third, whether the refluxant is acid or nonacid, or mixed liquid-gas or gas only in composition, can be discerned by MII and not by manometry. Finally, MII can be combined with pH in the same 2.13-mm catheter, which allows prolonged ambulatory studies.
There were two unexpected findings in this study. First, <1% of REs were mixed (both liquid and gas) in composition compared with 68% in GERD patients during 24-h ambulatory MII pH. This may be related to our study being only recumbent and fasting. Second, there were 2.5-fold fewer MII-REs on the right than on the left side. This may have been a result of patient selection, because we selected patients who had frequent REs during standard manometry performed on the left side. However, we also found twofold more fasting REs on the left than on the right side in a previous report in a larger population of patients with severe GERD (3). Further studies should be done on a larger number of patients to determine whether these findings are consistent in a larger patient population.
A limitation to this report is that we included patients with only very severe GERD with severe endoscopic esophagitis who were already known to have repeated common cavities over a low basal LESp during standard manometry. This was intentional to maximize the opportunity to compare REs by the three study methods. Thus the results in this study may not apply to GERD populations with less severe disease.
Also, there are limitations to RE detection by MII. First, we found that frequent liquid REs may cause impedance to remain low (Fig. 2). Second, Barrett's mucosa has been found to have a low baseline impedance in the distal electrode pairs (8). A low baseline for either reason will make RE detection difficult. Third, analysis of MII-pH tracings is labor intensive. Further experience will determine whether MII is limited by these and other methodological shortcomings, and automated analysis will be necessary for the technique to have broad application.
In summary, MII accurately detects individual REs, even when they occur close together. The duration of MII-REs and common cavities is nearly identical and shorter than acid clearing primarily due to acid rereflux. MII confirms previous reports in fasting patients that gas-only REs predominate in the left recumbent posture and liquid-only REs on the right. Measurement characteristics of MII are more similar to the common cavity than the pH probe, although the qualitative and technical advantages of MII make it a better volume method than manometry in RE detection and clearing. The ability to combine pH and MII in the same 2.13-mm catheter is ideal for prolonged ambulatory studies. For example, the roles of acid rereflux, RE composition, and proximal extent of refluxant can be assessed in GERD patients with typical and atypical presentations.
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FOOTNOTES |
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Address for reprint requests and other correspondence: Steven S. Shay, Dept. of Gastroenterology/A30, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH, 44195-5164.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
April 10, 2002;10.1152/ajpgi.00470.2001
Received 5 November 2001; accepted in final form 1 April 2002.
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