Intraluminal impedance monitoring detects changes in the resistance to electrical current across adjacent electrodes positioned in a serial manner along a catheter. Multiple electrodes positioned along the axial length of the impedance catheter determine the proximal extent of a reflux event. It is capable of differentiating antegrade from retrograde bolus transit, as well as liquid from gas reflux. A pH electrode incorporated into the recording assembly allows for simultaneous detection of acid content. Patient tolerability is similar to conventional pH monitoring as this is a catheter- based system. Likewise, recording has been limited to 24 h.
There is considerable debate on the current role of pH-impedance testing in clinical practice[20-22]. As PPI use for GERD has increased, patients presenting with typical or atypical reflux symptoms in spite of PPI therapy, and without erosive esophagitis, often pose a diagnostic and management challenge. The association of non-acid reflux events with symptoms has been demonstrated in several studies[23-26]. Impedance-pH monitoring is the most sensitive technique for the detection of reflux events. As a result of the ability to detect, localize and classify reflux events as acidic, weakly-acidic or alkaline, simultaneously, pH-impedance testing has been posited as the future standard for reflux detection and monitoring. In addition, the more comprehensive reflux detection could guide more individualized therapy in patients based on their reflux profile as well as predict response to medical or surgical treatment[20,21].
Although theoretically superior to pH monitoring, the clinical utility of combined pH-impedance monitoring is still being investigated. Conventional pH testing has demonstrated high sensitivity and specificity in patients with GERD and erosive esophagitis. The chemical nature of non-acid reflux does not allow the presence of mucosal erosions to be used in the determination of sensitivity and specificity of impedance data. Therefore, studies that have examined the utility of impedance testing have relied upon symptom-reflux association methodology to support the clinical significance of non-acid reflux. As discussed below, substantial limitations for symptom-reflux association accuracy in the evaluation of acid reflux also apply to non-acid reflux. Furthermore, the reliance on symptom indices necessitates careful delineation of the specific symptom being evaluated. For instance, symptom association for regurgitation on PPI therapy is better detected by impedance testing than pH testing alone. However, the importance of non-acid reflux in generating symptoms of heartburn or chest pain is unclear. It has been demonstrated that the majority of persistent heartburn or chest pain events on PPI therapy are not related to either acid or non-acid reflux[26,28]. Extra-esophageal symptoms of globus, asthma and hoarseness might occur independent of individual reflux events and thus are inappropriate for reflux-symptom association analysis. GERD is often considered as a cause of chronic cough. Although studies have shown symptom correlation between cough and GERD, 50% of the cough episodes precede the individual reflux events, which demonstrates that cough-induced reflux occurs as often as reflux-induced cough.
Further difficulties in substantiating a role for pH-impedance monitoring arise from the absence of highly effective, pharmacological therapies for non-acid reflux. Limited studies have used baclofen and baclofen analogs that inhibit transient LES relaxation. Surgical fundoplication is a more definitive means of arresting both acid and non-acid reflux, and ongoing studies are examining the use of pH-impedance results in predicting postoperative outcomes in refractory reflux patients. Additional limitations of impedance monitoring include low baseline impedance values generated by the mucosa of Barrett’s esophagus and esophagitis, which make detection of liquid reflux problematic in such circumstances. Inaccuracies in the current versions of automated analysis software require careful and time consuming manual data correction.
As a result of the ability to characterize acidity and determine number, duration, and location of reflux events, the majority of research using pH-impedance has focused on the challenges associated with diagnosing and treating NERD. A recent small study has evaluated 16 NERD patients with both pH-impedance and combined multiple pH monitoring in an effort to assess changes in reflux acidity and sensitivity to reflux events. Compared to multiple site pH testing (at three locations), pH-impedance monitoring showed a small increase in sensitivity in detecting proximal reflux events. The authors reported that 30% of all distal acid reflux events became weakly acidic in the proximal esophagus, and a third of these events resulted in symptoms. Although the sample size was small, the results lend support to the concept of hypersensitivity in the proximal esophagus in a subset of NERD patients[31,32].
In a much larger study, Savarino et al have evaluated the diagnostic utility of pH-impedance monitoring in 150 patients with NERD off PPI therapy. Among patients with normal distal esophageal acid exposure time, they found similar positive symptom associations for patients with acid reflux (15%) and non-acid reflux (12%). Twenty-six per cent of this group had a negative symptom association and were considered functional heartburn patients. The classification of patients with hypersensitive esophagus accorded by pH-impedance results (normal acid exposure time, positive symptom association) reduced the number of patients that would have been classified as having functional disease by 40%. However, overall 87% of the 150 NERD patients had acid reflux identified as the etiology of their symptoms.
Impedance pH monitoring has also been used to compare reflux patterns between patients with erosive esophagitis and NERD[34,35]. In a small study of 26 patients, evenly split between NERD and erosive disease, pH-impedance monitoring did not reveal significant differences in mean reflux duration or the incidence of acid or non-acid reflux episodes. When stratified by type of reflux episode, patients with erosive disease did have slightly more liquid (mean 9 ± 2 vs 5 ± 1, P = 0.07) and acid (mean 9 ± 2 vs 4 ± 1, P = 0.048) reflux episodes in the supine position. Overall, pH-impedance could not discriminate between NERD and erosive esophagitis but this likely reflects the limited power of the sample size. In another study, Savarino et al have compared a cohort of GERD patients with erosive and non-erosive disease with a control population and demonstrated increased acid exposure times, and frequencies of acid reflux events as well as proximal esophageal reflux extension, in both GERD subsets. Patients with erosive disease had a higher frequency and increased proximal migration of acid reflux events. Notably, the frequency of non-acid reflux events and their association with symptoms were similar in both erosive and non-erosive disease. Overall, the results of these studies lend further support to the argument for monitoring both acid and non-acid reflux episodes in further characterizing GERD and potentially directing management. However, the increased diagnostic yield of pH impedance over pH monitoring alone was limited and neither study has demonstrated that the increased detection results in improved patient therapeutic outcomes.
There has also been debate about whether pH-impedance monitoring should be performed on or off PPI therapy. This has recently been addressed in a small prospective study of patients with continued GERD symptoms on twice daily PPI therapy. Using a randomized, crossover study design, combined 24-h pH-impedance monitoring was performed on (twice daily) and off PPI therapy for 7 d. Neither the number nor extent of reflux episodes was affected by PPI use. There were significantly more acidic reflux episodes off PPI therapy and more weakly acidic episodes on PPI therapy. However, there was lack of concordance between the SAP for both measurements, which was likely due to the small sample size of the study.
Ultimately, the benefit of using pH-impedance monitoring in routine clinical practice depends upon its ability to guide effective medical and surgical management. A prospective series of 12 patients in Switzerland evaluated using pH-impedance monitoring before and after anti-reflux surgery (mesh-augmented hiatoplasty). Although the sample size was small, the authors found that multi-channel intraluminal pH-impedance monitoring significantly increased the number of reflux episodes detected before and after surgery compared to pH testing alone. There were also more patients identified as having a positive SI in the pH-impedance group. The study has found that pH-impedance monitoring provides increased data compared to pH testing alone, however, whether this information favorably affects management and long-term patient outcomes is yet to be determined. Future therapeutic trials using inhibitors of transient LES relaxation should provide valuable insights into the clinical significance of non-acid reflux.