Digestive and Liver Disease
Volume 40, Issue 3 , Pages 161-166, March 2008

Esophageal impedance–pH monitoring

  • D. Sifrim

      Affiliations

    • Corresponding Author InformationCorresponding author at: Faculty of Medicine K.U. Leuven, Lab G-I Physiopathology, O&N Gasthuisberg, 7th floor, Herestraat 49, 3000 Leuven, Belgium. Tel.: +32 16 345752; fax: +32 16 345939.
    • ,
  • F. Fornari

Centre for Gastroenterological Research K.U. Leuven, Belgium

Received 20 August 2007; accepted 31 October 2007. published online 14 December 2007.

Article Outline

Abstract 

Classical techniques like endoscopy and esophageal pH-metry are routinely used to study patients with symptoms related to gastroesophageal reflux disease (GERD). Although these techniques have been useful over the years both for diagnosis and therapeutic guidance, there are still many patients with typical or atypical GERD symptoms with normal endoscopy and pH-metry that do not respond adequately to antisecretory therapy. Ambulatory esophageal impedance–pH monitoring is a new technique that can be used to evaluate all types of gastroesophageal reflux, achieving higher rates of sensitivity and specificity than standard techniques. This review describes esophageal impedance–pH monitoring, summarizing the current literature on validation studies and clinical application.

Keywords: Electric impedance, Gastroesophageal reflux disease, pH-metry

 

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1. Introduction 

Normal esophageal function allows food transport into the stomach, prevents reflux of gastric contents into the esophagus and facilitates esophageal clearance once reflux has occurred. Impaired esophageal function may underlie abnormally frequent reflux or may be the cause of poor clearance of damaging gastric material.

Classical techniques like endoscopy and ambulatory 24h pH-metry are routinely used to study patients with reflux-related symptoms. Although these techniques have been useful over the years both for diagnosis and therapeutic guidance, there are still many patients with typical or atypical gastroesophageal reflux disease (GERD) symptoms with normal endoscopy and pH-metry that do not respond adequately to antisecretory therapy. Upper endoscopy is largely used to investigate patients with GERD symptoms but its sensitivity to detect reflux-related mucosal injury is limited. 24h pH-metry was considered the gold standard for reflux detection. However, pH monitoring does not detect all types of reflux, particularly when little or no acid is present in the refluxate. This is the case in patients after eating, before the gastric contents have become acidified, and it also applies to patients undergoing anti-secretory therapy.

Combined multichannel intraluminal impedance and pH monitoring is a new technique that can be used to evaluate both bolus transport and all types of reflux (acid, weakly acidic and weakly alkaline), without radiation hazards. This review describes impedance–pH monitoring and summarises the current literature on validation studies with reproducibility tests and comparisons with other diagnostic techniques. In addition, normal impedance–pH values and association between impedance patterns and GERD symptoms are commented.

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2. Technique 

Silny first described the technique for measuring intraluminal impedance in 1991 [1]. Intraluminal electrical impedance is based on the measurement of electrical impedance between closely arranged electrodes during a bolus passage using an intraluminal probe. Cylindrical shaped metal electrodes are mounted on a thin plastic catheter. Each neighbouring pair of electrodes (impedance segment) is connected to an impedance voltage transducer, which delivers a measuring current. The output of the measurement represents the electrical impedance around the catheter in the section between the pair of electrodes. The impedance is inversely proportional to the electrical conductivity of the luminal contents and the cross-sectional area between the two electrodes. Air has a low conductivity and yields an impedance increase, while swallowed or refluxed material has a high conductivity and yields an impedance drop. Furthermore, luminal dilation, i.e. induced by a bolus entry in the measuring segment, results in an impedance drop, whereas luminal narrowing, i.e. during an occlusive contraction causes an impedance increase [2]. Changes in temporal–spatial patterns in impedance are identified at various levels within the oesophagus, allowing differentiation between antegrade (i.e., swallow) and retrograde (i.e., reflux) bolus movement [3].

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3. Validation studies 

Animal and human validation studies were performed to assess the accuracy of impedance–pH monitoring for reflux detection. Impedance changes associated with esophageal retrograde flow of gas or liquid were first investigated in sedated cats [4]. An impedance catheter was placed in the distal esophagus and the stomach was loaded with air or with acidified contrast solution. Videofluoroscopy and impedance were recorded until gastroesophageal reflux occurred. Fluoroscopy performed as the stomach was being distended showed that air suddenly escaped into the esophagus. The sudden entrance of air into the oesophagus was recorded as a very rapid, aboral increase in impedance in all esophageal channels. Fluoroscopy, performed as the stomach was being filled and distended with a radio-opaque acidic solution, showed that liquid suddenly escaped into the oesophagus. Gastroesophageal reflux of liquid was recorded as an oral, slow sequential drop in impedance starting at the most distal measuring segment. Impedance returned progressively to baseline values simultaneously with the peristaltic stripping wave observed under fluoroscopy.

A recent study compared gastroesophageal reflux measured with impedance and manometry (common cavity) to pH monitoring. Only 19% of reflux episodes were detected simultaneously by all three methods. Impedance detected more reflux (96%) than manometry (76%) or pH probe (28%) [5]. Another study compared reflux detection between impedance–pH and pH alone. The use of pH alone was very sensitive for the detection of acid reflux but had lower specificity compared with impedance–pH monitoring. Overdiagnosis of abnormal acid exposure was observed in up to 22% of patients using only pH testing [6].

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4. Gastroesophageal reflux detection 

4.1. Patterns 

Impedance–pH monitoring allows detection of most reflux events and distinction between acid, weakly acidic and weakly alkaline reflux. Furthermore, this combined technique allows assessment of duration and proximal extent of a reflux event. A recent consensus report provided a detailed nomenclature for reflux patterns detected by impedance–pH monitoring [3].

Gastroesophageal reflux of liquid is detected as an orally progressing drop in impedance, starting at the level of the distal esophagus and propagating to more proximal impedance measuring segments. Impedance is very sensitive for detection of small volumes of liquid and similar drops in impedance are observed with boluses of 1ml and 10ml [7]. Therefore, so far, the intraluminal impedance technique cannot estimate the volume of the refluxate.

Gastroesophageal reflux of gas is detected as an almost simultaneous or rapidly orally progressing rise in esophageal impedance in at least two consecutive esophageal impedance channels. When reflux of gas occurs in the upright position, intraluminal air is better detected by impedance recordings in the most proximal esophagus.

Reflux events are diagnosed by impedance while their acidity is characterised by simultaneous pH monitoring as follows [3]: “acid reflux” is defined as a reflux episode that decreases esophageal pH across 4, or reflux that occurs when esophageal pH is already below 4. Reflux episodes that occur when the basal esophageal pH is already below 4 represent a special category of acid reflux, previously described as “re-reflux” and now re-named more accurately as “superimposed acid reflux”. This is an important phenomenon underlying the delay in esophageal clearance, particularly in patients with hiatal hernia [8].

The literature contains different definitions of the term “non-acid” reflux. However, the definition should be based on the pH of the refluxate, as defined chemically. In cases where the pH falls by at least 1 unit, but does not fall below 4, it is considered the term “weakly acidic reflux”. A pH of 7 should be the cut off between “weakly acidic” and “non-acid reflux”. The question arises as to whether a reflux episode should be defined as “non-acid reflux” because it increases the esophageal pH, or “weakly acidic reflux”, as the refluxate content is still acidic. A consensus report proposed that the term “weakly alkaline reflux” should be reserved for reflux episodes during which nadir esophageal pH does not drop below 7. Therefore, the previous description “non-acid reflux” can be renamed as “weakly alkaline reflux” that by definition is a very exceptional event.

The influences of a meal and body posture on reflux composition were recently assessed in GERD patients and healthy subjects using impedance–pH monitoring combined with esophageal manometry. Irrespective of the presence of GERD, reflux episodes were nearly always liquid-only when the subjects were laid on the right side, where the esophagogastric junction may be below fluid. In contrast, most of reflux on the left side and upright were gas-only or liquid and gas [9].

Nocturnal reflux has been recently re-assessed using impedance–pH monitoring in healthy subjects and GERD patients [10]. Most acid and non-acid nocturnal reflux episodes are preceded by esophageal antegrade bolus transport episodes suggesting periods of short arousal preceding reflux.

Impedance–pH monitoring is currently proposed for laryngo-pharyngeal reflux (LPR) detection. In healthy subjects evaluated with impedance–pH monitoring most of LPR events were weakly acidic, even if they were shown to be acidic in the distal esophagus [11]. Impedance sensors at the proximal margin of the upper esophageal sphincter yield the highest detection rate of LPR, irrespective of subject posture. With the sensors in this anatomical position, impedance–pH was able to detect pharyngeal gas reflux events, as well as acid and non-acid reflux as small as 0.1ml [12], [13].

4.2. Normal values and reproducibility 

The prevalence of different types of reflux (acid, weakly acidic and weakly alkaline reflux) in healthy adult subjects has been assessed using ambulatory impedance–pH monitoring. A first study investigated 28 healthy controls having a standard liquid meal. In this study, the total rate of reflux episodes was around 40/24h of which one third where acid and two thirds were weakly acidic and weakly alkaline [14]. Similar findings were obtained in a second study where the subjects could eat their habitual solid liquid meals [15]. More recently, normal values of ambulatory 24h impedance–pH monitoring were obtained in multicenter studies from adult American and European subjects [16], [17]. In addition, a single-center study defined normal values of impedance–pH in subjects eating a Mediterranean diet [18]. These values can now be used in clinical and research settings for comparison with GERD patients.

Normal impedance–pH values and sensitivity tests have been assessed also in infants. A study described the characteristics of reflux in 21 healthy preterm neonates completely asymptomatic, receiving nasogastric feeding in the neonatology recovery unit [19]. This study provides reference values for comparisons with pathologic conditions in preterm neonates. The sensitivity of impedance–pH monitoring to evaluate reflux in children off and on acid suppressive therapy was compared with that of only-pH monitoring. The sensitivity of impedance equals that of only-pH in untreated patients but was superior in treated patients. However, only-pH detected reflux events were numerous and should be included in impedance–pH analysis [20].

Good reproducibility of impedance–pH monitoring has recently been demonstrated in healthy subjects in standardised, stationary, short-lasting postprandial studies [21]. The multicenter European study also demonstrated good reproducibility of 24h impedance–pH monitoring [17].

4.3. Association of different patterns of reflux, detected by impedance–pH monitoring, with symptoms 

In patients off proton pump inhibitors (PPI) therapy, heartburn, acid taste, and regurgitation were associated with both acid and weakly acidic reflux events during a stationary postprandial impedance–pH study [22]. The presence of any symptom was more common during acid reflux than weakly acidic reflux. When specific symptoms were analysed separately, heartburn and acid taste were more commonly linked to acid reflux and regurgitation was reported with similar frequency during acid and weakly acidic episodes. In a 24h ambulatory impedance–pH study including 30 patients with GERD, 200 heartburn episodes were analysed. In half of them, reflux occurred in the preceding 2min interval, i.e. reflux+ symptom+ (R+S+). The majority (88%) of R+S+ involved acid reflux events, whereas weakly acidic accounted for only 12% of all R+S+ [23]. In patients with chronic unexplained cough studied off PPI therapy, ambulatory pressure–pH–impedance monitoring showed a subgroup of patients with chronic cough clearly associated with weakly acidic events [24]. It has been shown that when both pH and impedance parameters were used to identify reflux, a higher proportion of GERD patients off PPI therapy had a positive symptom association than when they were studied with pH-metry alone [25].

In patients on PPI therapy, a stationary postprandial impedance–pH study documented a striking decrease in the amount of acid reflux, with continuing postprandial reflux of weakly acidic gastric contents. Heartburn, the main symptom accompanying acid and weakly acidic reflux in the untreated state, was replaced by regurgitation, which became the predominant symptom during acid-suppressing therapy [22]. Studies using 24h impedance–pH monitoring in GERD patients on PPI therapy showed that acid reflux (incomplete acid secretion blockade by PPIs) is associated in 7–28% of persistent symptoms, weakly acidic reflux precedes 30–40% of symptoms which were not preceded by any reflux in 30–60% of cases [26], [27]. Patients in which symptoms were associated with weakly acidic reflux did not have an increased number of reflux events, suggesting hypersensitivity of the esophagus to less acidic refluxate [26].

Studies using impedance–pH monitoring have also shown that whether or not a reflux episode is perceived as a symptom is determined by proximal extent of the refluxate, nadir pH, magnitude of the drop in pH as well as by volume and acid clearance time. Reflux episodes inducing regurgitation have a more proximal extent than episodes inducing heartburn. Furthermore, acidic gas reflux without a liquid component or “acid vapour” can be perceived as heartburn and regurgitation [28], [29].

An important issue that rises with the use of impedance–pH monitoring is the role of weakly acid reflux on symptom genesis. The association of this type of reflux with extra-esophageal symptoms has been evaluated in infants with cardiorespiratory symptoms and more recently in adult patients with chronic cough and persistent globus.

Like in healthy babies, weakly acidic reflux is significantly more frequent than acid reflux in infants with cardiorespiratory symptoms. In 22 infants with recurrent regurgitation or pulmonary problems impedance–pH monitoring showed that 90% of reflux events were weakly acidic [30]. In that same group of infants with respiratory symptoms, 49 of 165 apnea episodes were accompanied by reflux episodes being 77% of these, weakly acidic [31]. Similar findings were recently reported in infants with apnea of prematurity, suggesting an association between such symptom and weakly acid reflux, as well as with reflux events longer than 30s [32]. However, the causal relationship between weakly acidic reflux and pediatric respiratory symptoms remains controversial. Another study in 19 infants with apnea of prematurity could not confirm the previous finding. A temporal relationship between reflux and a cardiorespiratory event was considered present if both commenced within 20s of each other. Although apnea and reflux were common in these infants, with few exceptions, did not seem to be temporally related. In addition, only a minority of apneas (3.5%) was associated with reflux reaching the pharyngeal level [33]. Another study could not find a role for weakly acidic reflux in the frequency association with apnea [34].

A recent study using impedance–pH assessed reflux in 50 children with typical or atypical GERD symptoms [35], but normal values for comparison with this population are still lacking.

Acid reflux is one of the most important causes of chronic cough. The response to acid suppression in these patients is not as good as in patients with heartburn but improvement with antireflux surgery has been reported, suggesting the involvement of a non-acidic gastric component in the refluxate. The association weakly acidic reflux-cough was studied in 28 patients with chronic cough using 24h ambulatory pressure–impedance–pH monitoring. Manometry was used for precise recognition of cough. A symptom association probability (SAP) analysis was performed for each type of reflux (acid and weakly acidic). This study allowed precise determination of the temporal association between cough and reflux and the identification of a subgroup of patients in which chronic cough was clearly associated with weakly acidic reflux [24]. A recent study using pressure–impedance–pH monitoring reinforced the above-mentioned observation. A positive association between cough and weakly acidic reflux was found in a significant subgroup of patients with unexplained chronic cough. In addition, impedance–pH-manometry identified patients with reflux-related cough that would have been disregarded using the standard diagnostic criteria for acid reflux [36].

Impedance–pH monitoring has been used to assess GERD-related laryngeal symptoms. A study in a small group of patients showed that gas reflux events with weak acidity appear to be more common among patients with reflux-attributed laryngeal lesions compared to GERD patients and controls [37]. Another study assessed reflux characteristics using impedance–pH monitoring in patients with globus despite PPI therapy. Patients with globus had a higher mean frequency of proximal reflux and the occurrence of weakly acidic reflux approached significance in predicting globus [38].

By assessing esophageal air transit with impedance, patients with dyspepsia have been shown to swallow air more frequently than controls and this is associated with an increased incidence of non-acid gaseous reflux [39].

4.4. Esophageal impedance–pH monitoring, treatments and outcomes 

Esophageal impedance–pH monitoring has opened the possibility to detect all types of reflux, achieving higher rates of sensitivity and specificity than standard techniques. Several studies recently assessed the effect of pharmacologic, endoscopic and surgical antireflux strategies on weakly acidic reflux.

Stationary and ambulatory impedance–pH studies showed that baclofen can reduce both acid and weakly acidic reflux by decreasing the number of transient LES relaxations [40], [41]. It is still unclear whether baclofen can improve persisting symptoms in patients on PPIs due to weakly acidic reflux. Oral alginate preparations are able to decrease the proximal extent of acid and weakly acidic reflux [42].

The endoscopic gastroplication (EndoCinch) was assessed using impedance–pH monitoring before and 3 months after the procedure. Total reflux exposure time, mean number of reflux episodes, mean volume clearance time and mean number of proximal reflux events were decreased 3 months after the procedure [43].

In the field of anti-reflux surgery, an initial case report of a patient with chronic cough followed for over one year post-fundoplication has documented total resolution of the cough and absence of continuing need for PPI therapy [44]. More recently, 17 patients resistant to PPIs with a positive symptom index for weakly acidic or acid reflux demonstrated by impedance–pH monitoring underwent Nissen fundoplication. After a follow-up of 14 months, 16 patients were asymptomatic or markedly improved [45]. Another study evaluated 36 GERD patients post-fundoplication by means of impedance–pH monitoring and compared these patients with 72 healthy subjects. The median number of reflux events over 24h was lower in operated patients and most of them were non-acid reflux. In addition, non-acid reflux events were significantly associated with symptoms after surgery in some patients [46].

Clinical controlled studies first performed in specialised centers with experience in impedance–pH monitoring and outcome data will ultimately define the usefulness of impedance for management of patients with symptom relationship to weakly acidic reflux.

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Practice points 


•Combined multichannel intraluminal impedance and pH monitoring is a new technique that can be used to evaluate both bolus transport and all types of reflux (acid, weakly acidic and weakly alkaline), without radiation hazards.

•With this technique, higher rates of sensitivity and specificity than standard techniques are obtained in the diagnosis of pathological gastroesophageal reflux (GER).

•The technique has also been used in the evaluation of atypical GER symptoms, in the assessment of the association of different patterns of reflux with symptoms, and in the evaluation of therapeutic outcome.

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Research agenda 


•Clinical controlled studies first performed in specialized centers with experience in impedance-pH monitoring and outcome data will ultimately define the usefulness of impedance for management of patients with symptom relationship to weakly acidic reflux.

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Conflict of interest statement 

None declared.

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References 

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PII: S1590-8658(07)00618-4

doi:10.1016/j.dld.2007.10.023

Digestive and Liver Disease
Volume 40, Issue 3 , Pages 161-166, March 2008

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