Esophageal multichannel intraluminal impedance testing

INTRODUCTION — Multichannel intraluminal impedance (MII) is a catheter-based method to detect intraluminal bolus movement within the esophagus. MII is performed in combination with manometry or pH testing. When combined with manometry, it provides information on the functional (ie, bolus transit) component of manometrically detected contractions. When combined with pH testing, it allows for the detection of gastroesophageal reflux independent of pH (ie, both acid and non-acid reflux).

This topic will review the principles, technique, and results of esophageal MII testing, and their clinical implications. Motility testing and high-resolution esophageal manometry are discussed in detail, separately. (See "High resolution manometry" and "Overview of gastrointestinal motility testing" and "Distal esophageal spasm and hypercontractile esophagus".)

PRINCIPLES OF IMPEDANCE TESTING — Impedance testing is based on the measurement of changes in resistance to alternating electrical current when a bolus passes by a pair of metallic rings mounted on a catheter. In an empty tubular organ such as the esophagus, the electrical current between the two rings is conducted by the few ions present in and on the mucosa. Liquid-containing boluses with an increased number of ions have a higher conductivity and, when entering the impedance-measuring segment, will lower the impedance to a nadir value. The impedance stays at its nadir as long as the bolus is present in the segment, returning to baseline once the bolus is cleared by a contraction. The contraction produces a slight increase in impedance above the baseline due to a decrease in luminal cross-section. Gas passing transiently by the impedance-measuring segments will produce a rapid and high (usually >3000 Ohms) rise in the impedance since it has poor electrical conductance.

Measuring impedance at multiple sites (multichannel) allows for determination of the direction of bolus movement based upon temporal differences in bolus entry and exit. Bolus entries progressing from proximal to distal indicate antegrade bolus movement, while bolus entries progressing from distal to proximal indicate retrograde bolus movement (waveform 1).

COMBINED MULTICHANNEL INTRALUMINAL IMPEDANCE AND MANOMETRY — Standard manometry does not demonstrate whether a contraction results in actual bolus passage. Combined multichannel intraluminal impedance with esophageal manometry (MII-EM) is a test of esophageal function as it provides information about both pressures and bolus transit within the esophagus.

Indications — The indications for MII-EM are similar to those for esophageal manometry (see "Overview of gastrointestinal motility testing", section on 'Esophagus'):

●Evaluation of patients with dysphagia, noncardiac chest pain, and/or heartburn/regurgitation

●Preoperative evaluation before antireflux surgery or endoscopic antireflux procedures

●Location of the lower esophageal sphincter (LES) prior to pH catheter placement

The role of MII-EM in the diagnosis of extra-esophageal disorders related to gastroesophageal reflux disease, such as chronic cough, has not been established [1]. (See "Laryngopharyngeal reflux in adults: Evaluation, diagnosis, and management".)

Patient protocol — Patients are asked to fast for four to six hours, after which the combined MII-EM catheter is inserted transnasally through the esophagus into the stomach. The procedure is performed in an outpatient setting. After successful catheter placement, 10 liquid and 10 viscous (applesauce) swallows are given, each 30 seconds apart.

The impedance of water can vary depending upon its source, leading to potential impedance artifacts. Normal saline is preferred over plain water since it has a standardized ionic concentration allowing reliable identification of bolus presence by impedance. Impedance testing with swallows of a viscous solution may be more sensitive than water swallowing in identifying esophageal dysmotility [2,3].

Technique — The LES is located by stationary pull-through technique, and the most distal sensor is placed in the high-pressure zone of the LES. The design of the catheter determines the location of the pressure and impedance-measuring segments. The conventional manometry nine-channel esophageal function testing catheter has five pressure sensors 5 cm apart and four impedance-measuring segments straddling the four proximal pressure sensors, allowing pressure measurements in the LES and at 5, 10, 15, and 20 cm above the LES. Impedance-measuring segments are centered at 5, 10, 15, and 20 cm above the LES. High-resolution impedance manometry systems use multiple pressure and impedance sites separated by 1 to 2 cm to more closely view pressure and bolus transit from pharynx to stomach. Data analysis is performed using dedicated software. (See "High resolution manometry", section on 'Technique' and "Overview of gastrointestinal motility testing", section on 'Esophageal manometry'.)

Impedance results parameters — Impedance measurements allow identification of the bolus in a given segment of the esophagus. Bolus entry is considered at the 50 percent drop in impedance from baseline relative to nadir and bolus exit at the 50 percent recovery point from nadir to baseline. Measuring bolus presence at different levels in the esophagus individual swallows are classified by MII as showing:

●Complete bolus transit – Bolus transit is defined as complete if bolus entry occurs at the most proximal site (20 cm above the LES) and bolus exit points are recorded in all three distal impedance-measuring sites (ie, 15, 10, and 5 cm above the LES).

●Incomplete bolus transit – Bolus transit is defined as incomplete if bolus entry occurs at the most proximal site (20 cm above the LES) and bolus exit is not identified at any one of the three distal impedance-measuring sites.

The number of swallows with complete and incomplete bolus transit can be used to assess bolus transit.

●Normal esophageal bolus transit – At least 70 percent of individual liquid swallows have complete bolus transit and at least 60 percent of individual viscous swallows have complete bolus transit.

●Esophageal transit abnormality – An esophageal transit abnormality is considered to be present if 30 percent or more of liquid swallows have incomplete bolus transit or if 40 percent or more of viscous swallows have incomplete bolus transit [4].

The interpretation of the manometric pressure and other parameters obtained by conventional and high-resolution manometry is discussed in detail, separately. (See "Distal esophageal spasm and hypercontractile esophagus" and "High resolution manometry".)

Clinical application — Combined MII-EM has a high sensitivity for detection of esophageal motility disorders. In patients with nonobstructive and postoperative dysphagia, MII-EM may have a higher sensitivity for detection of an underlying bolus transit abnormality as compared with manometry alone [2,4,5]. (See 'Impedance results parameters' above.)

Functional information provided by MII-EM allows for categorization of transit abnormalities into those with a pressure-only defect and those with a pressure and bolus transit defect (table 1). Studies in patients with esophageal motility abnormalities suggest that patients with achalasia or scleroderma have abnormal bolus transit, while over 95 percent of patients with normal manometry, nutcracker esophagus, or isolated LES abnormalities (ie, hypertensive LES, hypotensive LES, or poorly relaxing LES) have normal bolus transit [6,7].

Combined MII-EM can also assess the degree of functional defect in patients with manometrically defined ineffective esophageal motility and distal esophageal spasm [8,9]. However, additional studies are needed to evaluate the prognostic values of pressure and bolus transit abnormalities detected on MII-EM.

COMBINED MULTICHANNEL INTRALUMINAL IMPEDANCE AND PH — The addition of multichannel intraluminal impedance (MII) to pH testing has the advantage of detection of non-acid gastroesophageal reflux (GER) in addition to acid reflux.

Indications

●To quantify and characterize GER, especially in patients with an incomplete or no response to acid-suppressive therapy with a proton pump inhibitor (PPI) and who have normal endoscopic findings [10]. (See "Approach to refractory gastroesophageal reflux disease in adults", section on 'Esophageal impedance pH testing'.)

●To evaluate patients with atypical GER symptoms (eg, chronic cough, dysphonia/hoarseness, globus pharyngeus, or nonproductive throat clearing) [11-13]. (See "Laryngopharyngeal reflux in adults: Evaluation, diagnosis, and management" and "Globus sensation".)

Patient protocol — Patients are instructed to fast for four to six hours prior to probe insertion and to have a "usual" day following probe insertion. Patients are provided a diary to record the time and content of meals, time of upright and recumbent periods, time of administration of acid-suppressive medication, and time of symptoms and other relevant events (eg, correction of catheter position, disconnection of the skin electrode). Relevant symptoms should be agreed upon before the study begins and can be assigned to "event" buttons on the recording device, which should then be pressed with the occurrence of each symptom.

There are no clear guidelines on whether or not diet restrictions should be given, and the practice varies by center. We encourage patients to induce as many symptoms as they can by either ingesting foods and/or doing activities known to produce symptoms. The following day the patient returns the logger and diary, and data are downloaded.

Testing on or off proton pump inhibitors — The decision to perform combined MII and pH (MII-pH) testing on or off proton pump inhibitor (PPI) therapy should be based on the underlying indication for testing. In patients with refractory GER disease (GERD) symptoms, MII-pH testing is intended to detect weakly acidic (non-acid) reflux as a cause of ongoing symptoms [10,14,15]. Therefore, PPI therapy is usually continued for the examination. In such patients, we suggest high-dose acid-suppressive therapy (ie, a PPI at least twice daily before meals) for at least one week before combined MII-pH testing. Patients taking acid-suppressive therapy should be instructed to take the medications as prescribed, even on the day of testing. In patients in whom it is unclear if GERD is the cause of their symptoms, we perform MII-pH testing off PPIs to optimize the chance of detecting reflux events.

Technique — The combined MII-pH probe is placed transnasally into the esophagus. Available probes (6 impedance probes and 2 pH probes) are 2.1 mm in diameter (similar to conventional pH probes) and allow for pH sensors to be placed 5 cm above the lower esophageal sphincter (LES) and 10 cm below the LES, with impedance-measuring segments at 3, 5, 7, and 9 cm above the LES in the distal esophagus and at 15 and 17 cm above the LES in the proximal esophagus (figure 1). While these probes are preferred to investigate patients on PPI therapy, there are also probes with only 6 impedance-measuring segments and one pH sensor (placed at 5 cm above the LES). The later probe is sufficient when performing measurement off PPI therapy. Data analysis is performed using dedicated software. The principles of data analysis are the same regardless of which system is used.

Impedance-pH results parameters — In addition to providing information on conventional pH parameters, combined MII-pH monitoring also provides information on the following parameters:

Refluxate composition — Reflux episodes are classified by MII as containing gas, liquid, or both, based upon different impedance patterns. Air conducts electricity poorly and therefore has very high impedance, whereas liquid gastric contents have low impedance. Mixed reflux events are a combination of both a liquid and gas pattern.

Proximal extent of reflux — The proximal extent of a reflux event is defined by the most proximal impedance-measuring segment reached by the liquid component of the reflux episode. Gas reflux events are not assigned a proximal extent since they typically penetrate the upper esophageal sphincter and are eliminated.

Number of acid and non-acid reflux episodes — Combined MII-pH defines the number of MII-GER episodes as the total number of MII-detected episodes.

Refluxate contact time — Refluxate presence time is defined as the total amount of time (absolute or percent of the study period) liquid-containing refluxate is detected by the impedance-measuring segment located at 5 cm above the LES.

Refluxate clearance time — Reflux clearance time is defined as the average duration that liquid-containing MII-refluxate is present 5 cm above the LES.

Reflux pH — The abovementioned parameters are further categorized into acid and non-acid based upon the pH changes recorded at the time when the reflux occurred. According to the position of the subject at the time the GER occurs, these parameters are further separated into upright and recumbent.

●An acid reflux event is defined as an event during which there is a drop of pH to below 4.

●Non-acid reflux is defined as an event during which the pH stays above 4 (figure 2).

●Weakly acidic (non-acid) reflux is used to define reflux episodes with pH 4 to 7. Weakly alkaline is defined as reflux episodes with pH >7 [16]. Since weakly alkaline reflux episodes (pH >7) are rare, from a practical point of view the terms "weakly acidic" and "non-acid" describe the same event (ie, reflux episodes with pH >4).

Interpretation of results

Reference values — Overall study interpretation is based initially upon normative data from healthy volunteers [17]. In the postprandial period, acid-suppressive therapy primarily changes the ratio of acid versus non-acid reflux episodes [18]. Acid-suppressive therapy also decreases the total number of reflux episodes, presumably by reducing the total amount of gastric secretion [19,20]. As a result, different normal values are used when interpreting the total number of reflux episodes in patients "off" and "on" acid-suppressive therapy (table 2).

Symptom correlation measures — The main parameter used to interpret MII-pH monitoring studies is the association of symptoms with GER episodes (acid and non-acid). Two main indices have been used to assess this association.

●Symptom index (SI) – The SI represents the number of symptoms associated with reflux occurring in the preceding five-minute interval divided by the total number of symptoms recorded by a patient during the monitoring period expressed in percent. Patients with a positive test (SI ≥50 percent) are considered to have symptomatic GER on PPI therapy. By contrast, patients with SI <50 percent are considered to have a negative study and persistent symptoms on PPI therapy are due to causes other than GER. However, the validity of these cutoffs has not been established.

●Symptom association probability (SAP) – For the calculation of the SAP, the total measuring time is subdivided into two-minute intervals. A contingency table with four fields (number of intervals with GER and symptoms, number of intervals with GER without symptoms, number of intervals without GER and with symptoms, and number of intervals without both GER and symptoms) is used to assess correlation with the Fisher exact test [21]. A positive SAP (>95 percent) is interpreted as a good temporal association between GER and the recorded symptom.

Clinical application — MII-pH has a high sensitivity for detecting all types of reflux episodes. It is primarily used to evaluate patients with persistent symptoms despite PPI therapy in order to clarify the association of symptoms with reflux events [16,22]. Studies using combined MII-pH have demonstrated that approximately one-half of patients with persistent symptoms on PPI therapy do not have a temporal correlation between their symptoms and any type of reflux [1,13,23-29]. In addition, approximately 40 percent of patients with persistent symptoms on PPI therapy have a temporal association between their symptoms and reflux, primarily of the non-acid type. However, whether the improved understanding of symptoms to reflux and non-reflux events translates into better health outcomes has not been well established. (See 'Combined multichannel intraluminal impedance and pH' above and "Non-acid reflux: Clinical manifestations, diagnosis, and management", section on 'Diagnostic evaluation'.)

COMPLICATIONS AND CONTRAINDICATIONS — Complications of multichannel intraluminal impedance testing are extremely rare but could include infection, bleeding, and trauma to the nasopharynx or esophagus. Relative contraindications for placement of a transnasal MII catheter include prior nasal surgery or trauma, coagulopathy, and the concurrent use of anticoagulants [30]. Safety data on the use of impedance in patients with implantable cardiac defibrillators and pacemakers are lacking. However, interference of pacemakers/automatic implantable cardioverter-defibrillators with the impedance measurement or triggering of defibrillation has not been reported.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Esophageal manometry and pH testing".)

SUMMARY AND RECOMMENDATIONS

●Multichannel intraluminal impedance (MII) is a catheter-based method to detect intraluminal bolus movement within the esophagus. MII is performed in combination with manometry or pH testing. (See 'Introduction' above and 'Principles of impedance testing' above.)

●MII combined with esophageal manometry (MII-EM) provides information about both pressures and bolus transit within the esophagus. Indications for MII-EM include evaluation of patients with dysphagia, noncardiac chest pain, heartburn/regurgitation, and preoperative evaluation before antireflux surgery or endoscopic antireflux procedures. (See 'Indications' above and 'Clinical application' above.)

●Swallows are classified by MII-EM as showing complete bolus transit if bolus entry occurs at the most proximal site (20 cm above the lower esophageal sphincter [LES]) and bolus exit points are recorded in all three distal impedance-measuring sites (ie, 15, 10, and 5 cm above the LES), and incomplete bolus transit if bolus exit is not identified at any one of the three distal impedance-measuring sites. An esophageal transit abnormality is considered to be present if 30 percent or more of liquid swallows have incomplete bolus transit or if 40 percent or more of viscous swallows have incomplete bolus transit. (See 'Impedance results parameters' above.)

●Combined MII and pH (MII-pH) testing can detect both acid and non-acid gastroesophageal reflux (GER). Indications for MII-pH include quantification and characterization of GER, especially in patients with an incomplete or no response to acid-suppressive therapy with a proton pump inhibitor (PPI) and who have normal endoscopic findings and evaluation of atypical GER symptoms (eg, chronic cough). (See 'Indications' above and 'Clinical application' above.)

●The decision to perform MII-pH testing on or off PPI therapy should be based on the underlying indication for testing. In patients with refractory GER disease (GERD) symptoms, MII-pH testing is intended to detect weakly acidic (non-acid) reflux as a cause of ongoing symptoms. In such patients we administer high-dose acid-suppressive therapy (ie, a PPI at least twice daily before meals) for at least one week before combined MII-pH testing. In patients in whom it is unclear if GERD is the cause of their symptoms, we perform MII-pH testing off PPIs to optimize the chance of detecting reflux events. (See 'Patient protocol' above.)

●In MII-pH studies, reflux presence, distribution, composition, and clearance are primarily detected by MII and characterized as acid versus non-acid based upon pH change. MII determines refluxate clearance time, while pH measures acid clearance time. Overall study interpretation is based initially upon normative data from healthy volunteers and association of symptoms with GER episodes (acid and non-acid). (See 'Impedance-pH results parameters' above.)

●Complications of MII testing include infection, bleeding, and trauma to the nasopharynx or esophagus. Relative contraindications for placement of a transnasal MII catheter include prior nasal surgery or trauma, coagulopathy, and the concurrent use of anticoagulants. (See 'Complications and contraindications' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Donald O Castell, MD, now deceased, who contributed to an earlier version of this topic review.