PRACTICAL GASTROENTEROLOGY • MARCH 2003 19 G astroesophageal reflux (GER) testing using com- bined MII-pH is a technique approved by the FDA in July 2002. MII can detect bolus volume presence independent of the pH of the refluxate. Thus, combined MII-pH represents a shift in the reflux-test- ing paradigm. GER of all types is detected by MII and is only characterized as acid or nonacid by its pH. Simultaneous measurements of manometry and impedance have been used to validate reflux detection by MII when reflux was identified by the presence of a manometrically defined “common cavity” (1). The ability of combined MII-pH to detect and characterize non-acid GER represents an important advance for clinical testing of non-acid reflux (2). It is not dependent on presence of bilirubin in the refluxate (a limitation of the Bilitec technique) (3), is not affected by gastric emptying time of an ingested mate- rial (a limitation of scintigraphic methods [4,5]) and does not require stationary-supine postures (a limita- tion of manometric measurements detecting common cavities [1]). Although non-acid reflux may have a limited role in development of erosive lesions within the esophagus it is quite likely to be clinically impor- tant in patients with early post-prandial symptoms, patients with persistent symptoms on acid suppressive therapy, patients with atypical (supraesophageal) symptoms and in infants. The interest for non-acid GER testing in infants is sustained by the fact that the acid output is decreased compared with adults and the feeding patterns (drinking milk or formula every 2–3 hours) maintain long periods of time with the stomach full and with buffering of intragastric acid concentra- tions (6,7,8). Combined MII-pH classifies GER by: (1) content of reflux into liquid, gas and mixed reflux events and (2) pH characteristics of the content into acid, non- acid, minor acid and acid re-reflux. Using multiple impedance measuring sites MII can also identify the height of the refluxate (i.e. most proximal impedance Combined MII and pH (MII-pH) USE OF MII IN EVALUATING PATIENTS WITH ESOPHAGEAL DISEASES, SERIES #3 Radu Tutuian, M.D., Research Fellow Gastroenterol- ogy and Donald O. Castell, M.D., Professor of Medi- cine, Division of Gastroenterology/Hepatology, Med- ical University of South Carolina, Charleston, SC. Radu Tutuian Donald O. Castell
Transcript
PRACTICAL GASTROENTEROLOGY • MARCH 2003 19
Gastroesophageal reflux (GER) testing using com-bined MII-pH is a technique approved by theFDA in July 2002. MII can detect bolus volume
presence independent of the pH of the refluxate. Thus,combined MII-pH represents a shift in the reflux-test-ing paradigm. GER of all types is detected by MII andis only characterized as acid or nonacid by its pH.Simultaneous measurements of manometry andimpedance have been used to validate reflux detectionby MII when reflux was identified by the presence ofa manometrically defined “common cavity” (1).
The ability of combined MII-pH to detect andcharacterize non-acid GER represents an importantadvance for clinical testing of non-acid reflux (2). It isnot dependent on presence of bilirubin in the refluxate(a limitation of the Bilitec technique) (3), is notaffected by gastric emptying time of an ingested mate-
rial (a limitation of scintigraphic methods [4,5]) anddoes not require stationary-supine postures (a limita-tion of manometric measurements detecting commoncavities [1]). Although non-acid reflux may have alimited role in development of erosive lesions withinthe esophagus it is quite likely to be clinically impor-tant in patients with early post-prandial symptoms,patients with persistent symptoms on acid suppressivet h e r a p y, patients with atypical (supraesophageal)symptoms and in infants. The interest for non-acidGER testing in infants is sustained by the fact that theacid output is decreased compared with adults and thefeeding patterns (drinking milk or formula every 2–3hours) maintain long periods of time with the stomachfull and with buffering of intragastric acid concentra-tions (6,7,8).
Combined MII-pH classifies GER by: (1) contentof reflux into liquid, gas and mixed reflux events and(2) pH characteristics of the content into acid, non-acid, minor acid and acid re-reflux. Using multipleimpedance measuring sites MII can also identify theheight of the refluxate (i.e. most proximal impedance
Combined MII and pH (MII-pH)
USE OF MII IN EVALUATING PATIENTS WITH ESOPHAGEAL DISEASES, SERIES #3
Radu Tutuian, M.D., Research Fellow Gastroenterol-ogy and Donald O. Castell, M.D., Professor of Medi-cine, Division of Gastroenterology/Hepatology, Med-ical University of South Carolina, Charleston, SC.
Radu Tutuian Donald O. Castell
channel in which GER impedance changes are noted).An acid MII-GER event is a MII-detected reflux eventin which a drop of pH from above 4.0 to below 4.0 isnoted (Figure 1a). Non-acid reflux is a MII-detectedevent during which the pH stays above 4.0 and doesnot drop more than 1 pH unit (Figure 1b). Minor acidreflux is a MII-detected reflux event during which pHstays above 4.0 but the pH drops more than 1 unit (Fig-ure 1c). An acid re-reflux event is another type of acid
reflux that occurs while intraesophageal pH is alreadybelow 4.0. It is detected by MII and the pH may ormay not go further below 4.0 (Figure 1d).
Currently available systems using combined MII-pH employ impedance rings mounted on pH catheters(Sandhill Scientific Inc., Highlands Ranch, CO). Thedimensions of combined MII-pH catheters are similarto those of traditional pH catheters (2.1 mm diameter)
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C D
Figure 1. Various types of reflux events detected by MII-pH. An acid MII-GER reflux event is a MII-detected reflux event in whicha drop of pH from above 4.0 to below 4.0 is noted (A). Non-acid reflux is a MII-detected reflux event during which the pH staysabove 4.0 and doesn’t drop more than 1 pH unit (B). Minor acid reflux is an MII detected reflux event during which pH staysabove 4.0 but the pH drops more than 1 unit (C). An acid re-reflux event is another type of acid reflux that occurs while intra-esophageal pH is below 4.0 and the pH may go further below 4.0 (D).
A B
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and therefore do not change patient comfort comparedto traditional pH testing. Different MII-pH catheterscan be used depending on the clinical scenario (Figure2). The “classic” 6MII-1pH assembly will readilydetect acid and non-acid reflux. Normative data forthis design have been established in a multicenterstudy (see below). A modified design 6MII-2pH(esophageal + gastric) catheter for use in patients ontherapy will concomitantly assess intragastric acidcontrol on therapy. Studies establishing normative dataon therapy are currently being conducted. A bifurcatedadjustable catheter (4MII-1pH + 2MII-1pH) may bepreferred to evaluate pharyngeal reflux concomitantly
with distal esophageal reflux. Normative data for thistechnique have yet to be established although our pre-vious experience with bifurcated pH probes revealsthat acid reflux rarely reaches the pharynx in normalvolunteers (9).
Normative data for the 6MII-1pH assembly havebeen established in a multicenter study involvingGraduate Hospital (Philadelphia), Cleveland Clinic,Mayo Clinic (Rochester), University of Southern Cal-ifornia (Los Angeles) and the Catholic University inLeuven, Belgium. Sixty healthy adult volunteersunderwent 24-h ambulatory MII-pH studies. Thisstudy indicates that normal volunteers have less non-acid reflux compared to acid-reflux, MII-detected acidrefluxate presence time (percent time) is significantlyless than percent time intraesophageal pH <4 andminor amounts and number of nonacid reflux events
USE OF MII IN EVALUATING PATIENTS WITH ESOPHAGEAL DISEASES, SERIES #3
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C
A
B
Figure 2. Placement of various combined MII-pH catheters:(A) “classic” 6MII-1pH probe placed relative to LES, (B) 6MII-2pH (esophageal and gastric pH) probe placementrelative to LES and (C) bifurcated 4MII-1pH + 2MII-1pHprobe placement relative to LES and UES
occur at nighttime in the supine position. Non-acidGER occurred predominantly in the 2-hour post-pran-dial periods. Furthermore 37% of distal (5 cm aboveLES) reflux episodes, either acid or non-acid, reach theproximal (15 cm above LES) esophagus in normal vol-unteers. In the same study it was also observed that
acid clearance (pH) time is different than acid bolus(MII) clearance time suggesting that neutralizing acidpH in the esophagus depends on other mechanisms(i.e. swallowing of saliva, mucosal characteristics,etc.) than only refluxate appearance and disappearancefrom the esophageal lumen.
Some of the advantages of com-bined MII-pH over traditional pH test-ing are supported by the followingreports. Studying the effects ofomeprazole on 2-h postprandial gas-troesophageal reflux Vela MF, et al(10) found that although the protonpump inhibitor dramatically reducedthe number of acid GER episodes thetotal number of MII-detected GERevents did not change but became pre-dominantly non-acid. This observa-tion underscores the effect of acidsuppressive therapy to shift the bal-ance of acid vs. non-acid reflux eventswithout influencing the total numberof GER events in the postprandialindividual (Figure 3A). Studying the
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Combined MII and pH (MII-pH)
A B
Figure 3. Effects of omeprazole and baclofen on post prandial reflux. Omeprazole shifts the balance of acid vs. non-acid refluxevents without influencing the total number of GER events while baclofen reduces the number of acid GER’s, number of non-acid GER’s and also the total number of GER events (adapted from Vela, et al., Gastroenterology 2001;120:1599-1606 and Vela,et al., Aliment Pharmacol Ther 2003 in press.)
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Figure 4. Patient with persistent regurgitation associated with non-acid GER,tested while on PPI therapy. Non-acid GER is detected by MII while pH remainsabove 4.0
effects of baclofen, a GABA antagonist that decreasesthe frequency of transient lower esophageal sphincterrelaxations (TLESR), Vela MF, et al (11) found thatthis medication reduced the number of all GERepisodes in a 2-h postprandial period; both acid and
non-acid GER. These studies suggestthat combined MII-pH should be thepreferred test to document reduction ofgastroesophageal reflux (Figure 3B).
Using combined MII-pH in clinicalpractice helps clarify symptoms attributedto GERD. To date using combined MII-pH in our motility laboratory we haveidentified different clinical applications,particularly related to patients with persis-tent symptoms on PPI therapy. One suchscenario involves non-acid reflux as acause of persistent regurgitation inpatients being considered for surg e r y(Figure 4). In other patients we have iden-tified gas reflux (belch) preceding the vastmajority of chest pain episodes leading totreatment with simethicon (Figure 5). Anincreased number of non-acid GERepisodes were identified in an 8-monthold infant with subglotic stenosis that wassubsequently referred for Nissen fundo-
plication. In yet another patient we were able to identifythat none of the persistent chest pain episodes on acidsuppressive therapy were related to any form of GER,clarifying for the patient that the cause of her symptomswas not related to GERD (Figure 6).
Current recommendations forGERD testing suggest an initial empirictrial of PPI’s in patients with symptomssuggestive of GERD (12). If patientsrespond to this trial the diagnosis isestablished and continuation of acidsuppressive therapy is recommended.Before MII-pH became availablepatients not responding to the PPI trialwould often undergo ambulatory pHtesting either while continuing therapyor after at least a 7 days “wash-out”period to evaluate if their symptomswere associated with GER. Thisapproach left the question of possiblenon-acid GER symptoms unresolved.Since combined MII-pH can identifyboth acid and non-acid GER we proposeusing MII-pH testing on therapy at this
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Combined MII and pH (MII-pH)
Figure 5. Patient in which persistent chest pain episodes were not associatedwith any type of reflux. The antegrade changes in impedance are produced byswallows.
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Figure 6. Patient with chest pain preceded by gas GER. Gas GER episodes areidentified by rapid increase in impedance to above 5000 Ohm in at least twochannels.
PRACTICAL GASTROENTEROLOGY • MARCH 200328
point in the GERD diagnostic algorithm. CombinedMII-pH (using esophageal and gastric pH) will iden-tify persistent symptoms associated with acid GER(suggesting inadequate acid control), symptoms asso-ciated with non-acid GER (suggesting the need for sur-gical, endoscopic or medical enforcing of the gastroe-sophageal barrier) or symptoms not associated withany type of reflux (suggesting that the patient’s symp-toms have a non-reflux etiology). This proposed GERdiagnostic algorithm is illustrated in Figure 7.
In summary combined MII-pH is a promising tech-nique using a new principle for gastroesophageal refluxtesting to identify liquid, gas, and mixed reflux and cat-egorize it into acid and non-acid. By its ability to betterdiscriminate GER and the association of symptomswith acid and non-acid GER combined MII-pH shouldbecome a useful tool in evaluating patients with persis-tent symptoms on acid suppressive therapy, patientswith atypical symptoms and possible GER in infants. ■
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