50

Esophageal pH and Impedance Measurement

Yvan Vandenplas, MD, PhD

Why monitor the pH and/or impedance in the
esophagus?
Gastroesophageal re ux (GER) is the invol-
untarypassage of gastric contents into the esoph-
agus. GER is a physiologic event occurring in
every individual several times during the day,
particularly after meals. Most re ux episodes
are asymptomatic, brief, and limited to the dis-
tal esophagus. GER may be a primary gastroin-
testinal motility disorder, but may be secondary
to other conditions, such as cow's milk protein
allergy. According to recent literature, cow's
milk protein allergy is a frequent cause of GER
during infancy.l? This review will discuss both
the advantages and the disadvantages of pH and
impedance techniques to measure GER.
The idea that pH measurement in the esoph-
agus may be of clinical importance started with
the observation that acid perfusion-induced heart-
burn coincides with a fall of intraesophageal pH
below4. This simple historical observation points
out one of the major pitfalls of pH monitoring: the
cutoff of "pH 4" was de ned to separate re ux
causing heartburn from re ux causing no heart-
burn. However, "heartburn" is only one of the
indications for pH monitoring. In other words: pH
4 may be an appropriate cutoff for heartburn, but
it has not been validated in patients with respira-
tory symptoms caused by GER. Esophagea! pH
monitoring is often considered as an investigation
technique studying esophageal motility, which it
obviously does not. In fact, esophageal pH metry
does even not measure GER. The technique simply
connected to a recorder. Impedance allows the
detection of the frequency, the esophageal height
and duration of re ux episodes, independent of
the pH of the re uxate. The term "intraluminal
impedance monitoring" is preferred because
of the concurrent measurement of impedance
from multiple intraluminal recording segments.
The method allows detection of GOR based on
changes in electrical resistance to electrical cur-
rent ow between two electrodes, when a liquid
and/or gas bolus moves between them (Table 1:
GER as measured by intraluminal impedance
monitoring). Impedance detects GER if there is a
sequential orally progressing drop in impedance
to less than 50% of baseline values starting dis-
tally [3 cm above the lower esophageal sphincter
(LES)] and propagating retrogradely to at least
the next two more proximal measuring segments.
According to the corresponding pH change,
impedance-detected re ux can be classi ed as
acid if the pH falls below 4 for at least 4 seconds
or, if pH was already below 4, as a decrease of at
Table 1 Symptoms of Gastroesophageal Retlux Discase
Symptoms/Signs
Vomiting
Regurgitation
Heartburnm
Epigastric pain
Chest pain
Dysphagia
Excessive crying/irritability
least 1 pH unit sustained for more than 4 seconds.
Weakly acidic re ux is de ned as a pH drop of at
least 1 pH unit sustained for more than 4 seconds
with basal pH remaining betvween 7 and 4. Re ux
is considered to be weakly alkaline when there is
impedance evidence of re ux but the pH does not
drop below 7. In many studies, weakly alkaline
and weakly acidic re ux are grouped together as
"nonacid re ux." Intraluminal air (which has a
very low electrical conductivity) provokes a rapid
and pronounced rise in impedance.
The main indications for esophageal pH moni-
toring are (1) clinical and laboratory research,
(2) clinical procedure to díagnose acid re ux,
especially in children presenting with atypical
GER manifestations (Table 2: symptoms accord-
ing to age), and (3) the evaluation of the ef cacy of
treatment of GERD on the frequency and duration
on the presence of acid in the esophagus. Intra-
luminal impedance (measuring ux of ions) will
measure more events than measurements of drops
in esophageal pH, since not all re ux is acid.
According to Age
Infants Children Adults
++ ++
+++ t
? ++ +++
++
++
? ++
+++ +

measures changes in esophagcal pH, not GER. The Anemia/melena/hematemesis +

commercialization of esophageal pH-monitoring Food refusal/feeding disturbancies/anorexia ++
Failure to thrive ++ +
devices in the 1980s changed the work-up of
GER substantially. It took many years to discover
Abnormal posturing/Sandifer's syndrome ++
Persisting hiccups +
advantages,but also pitfalls of pH monitoring. Dental erosions/water brush ?
The rst clinical tests were performed in the Hoarsencss/globus pharyngeus ? +
early 1960s by Miller. Electronic technology Persistent cough/aspiration pneumonia
has profoundly changed the practice of medicine, Wheezing/laryngitis/ear problems ++
Laryngomalacia/stridor/eroup + ++
principally through its ability to monitor, record,
and analyze large volumes of data. The introduc-
Chronic asthma/sinusitis ++ +
Laryngostenosis/vocal nodules problems + +
tion of computers has provided physicians with
ALTE/SIDSapnoea/desaturation
powerful tools to identify elusive and intermittent Bradycardia + ?
disorders, such as gastroesophageal re ux dis- Sleeping disturbancies + 4
case (GERD). As a consequence of this technical Impaired quality of life ++ ++ ++
Esophagitis + +
evolution, measurement of the impedance in the
Stenosis (+)
esophagus has become possible.
Barrett's/esophageal adenocarcinoma (+) +
The basic principle of impedance recording is
+++ = very common; ++ = common; + = possible; (+) = rare; - = absent;? = unknown.
identical to pH monitoring: registration of esoph-
ALTE = apparent life-threatening event; SIDS = sudden infant death syndrome
ageal events with a probe placed transnasally and
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 1394 PART VI / Diagnosis of Gastrointestinal Disorders

pH drift. A drift of less than 0.5 pH over the

Table 2 Detinition of Types of GER Dected by Intraluminal Impedanee
24-hour period is acceptable. Calibration needs
• Liquid GER: drop in impedance to less than 50% of baseline values to be corrected according to both room and body
Acid GER: pH falls below 4 for at least 4 s or, if pH was already below 4, decreases by at least 1 pH unit sustained temperatures.
for more than 4 s Both the device and the electrodes for imped-
Nonacid rettux: weakly acidic and alkaline GER ance testing are considerably more expensive
Weakly acidic re ux: pH drop of at least I pH unit sustained for more than 4 s with basal pH remaining between
than those used for pH metry. The impedance
7 and 4
Alkaline: pH does not drop below 7
clectrode also has one or two antimony sensors to
• Gas re ux: rapid and pronounced rise in impedance measure pH and rings (generally six) to measure
impedance. In older patients, the pH electrode
GER = gastrocsophageal re ux.
at the tip of the catheter measures gastric pH,
whereas the other pH antimony sensor measures
esophageal pH.
HARDWARE AND SOFTWARE: Owe to their smaller diameter, antimony
PEDIATRIC NEEDS (2.1 mm) or glass microelectrodes with external Location of the Electrode. The exactesophageal
reference electrodes (1.2 mm) are preferable in location of the pH electrode is of critical impor-
The Device infants. Antimony electrodes also exist with a tance regarding the number and duration of acid
diameter of about 1.5 mm for use in premature re ux episodes recorded. The closer the electrode
Purchase costs, system abilities, costs in use, num-
babies; these electrodes are too exible for use is located to the LES, the more acid re ux episodes
ber ofmeasurements,and durability of the material
in older babies. Glass electrodes have only one will be detected.15.1ó In adults, the electrode is, by
are factors to consider before purchasing equipment.
Impedance equipment is considerably more expen-
pH sensor. Antimony electrodes with multiple consensus, positioned 5 cm above the proximal
pH sensors may help to detect alkaline re ux epi- border of the LES. Also in adults, determination
sive than pH metry devices. O mportance for pedi-
atric use is a time indication on the display of the sodes, although measurement of esophageal pH of the position of the LES by means of astandard
is not recommended to detect alkaline re ux.3 stationary esophageal manometry study is gener-
recording device (ie, the number of data recorded,
Antimony electrodes with two sensors can also ally regarded as the optimum method for pH probe
the real time, and duration of the investigation) and
be helpful to evaluate the therapeutic ef cacy of localization. In children, several other methods
the protection of event marker(s) to avoid erroneous
acid-reducing medication: the esophageal sensor have been proposed to determine the location
use by the child.³ A system should refuse to work if
measures the incidence of acid re ux, while the of the electrode: uoroscopy, calculation of the
it has not been calibrated properly.
gastric sensor measures ef cacy of the medica- esophageal length according to Strobel's formula
There is no difference between a device for pH
or impedance recording: it is a "box" that stores
tion. Antimony is only poorly resistant to gastric [distance from thenose to the cardia =5+0.252
acid, but the fact that acid should be reduced or (length in cm)], and endoscopy. Ideally, as in
data in memory; at the end of the recording, the
minimized in these patients reduces the impact adults, the electrode should be sited in reference
device needs to be connected to a computer to
of this shortcoming. Thus, "Bilitec" (a technique to the manometrically determined LES. However,
read out the stored data. One of the advantages
measuring the presence of bile in the re uxed this has several inconveniences: (1) manometry
of pH and impedance monitoring is the possibil-
material) ând non-pH-dependent techniques, in infants and children is time consuming, rather
ity of obtaining an ambulatory recording, even
sueh as impedance, offer much more bene ts to invasive, or at least unpleasant and (2) this method
in young children. The device should be as small
mēasure nonacid re ux compared with using pH has the inconvenience that the electrode is located
and as light as possible. For pH metry, devices
electrodes with multiple electrodes. at a xed distance to the LES, whereas the length
no larger than a credit card, although of course a
Glass microelectrodes and, historically, also of the esophagus increases from less than 10 cm
little thicker, are now commercially available.
antimony electrodes need an external cutaneous in a newborn to over 25 cm in an adult. Moreover,
The utility of wireless technology for GER
reference electrode, which may cause erroneous manometry cannot be performed in all centers.
diagnosis has been validated in several studies,
measurement resulting from transmucosal poten- Therefore, the European Society for Pediatric Gas-
with improvements over catheter-based pH mon-
tial differences. If the environmental temperature troenterology, Hepatology, and Nutrition Work-
itoring in tolerability, accuracy, and sensitivity,
is high or the patient sweats a lot, the conductiv- ing Group recommended the use of uoroscopy
as well as the ability to record periods both off
ity of the contact gel will change, resulting in a to locate the electrode. The radiation involved is
and on therapy with proton pump inhibitors in a
less accurate conduction of the electric potential. minimal, and the method can be applied in each
single study. The major advantage of the wire-
Antimony electrodes with a diameter of about center. As the tip of the electrode moves with and
less capsule is the possibility to allow prolonged
2.0 mm containing an internal reference elec- during respiration, the tip should be positioned in
pH recording in more physiologic conditions. The
trode have been developed, providing adequate such a way that it overlies the third vertebral body
capsule sloughs off the wall of theesophagus in
results. This electrode is accurate, thin, exible, above the diaphragm throughout the respiration
7 to 10 days and passes out of the body naturally.
easy to place in the esophagus, and has become cycle (Figure l). Dislocation by a curled elec-
However, data in children are currently limited, 10
standard. Data obtained with a glass electrode trode is also prevented with uoroscopy. If the pH
correlate poorly with data obtained using an anti- device is exposed to X-rays, the data and calibra-
The pH and Impedance Electrode
mony electrode. In other words, normal ranges tion may be erased.
pH sensors or "electrodes" exist in several forms, obtained with glass electrodes cannot be used for For impedance it is also relevant to know
of which the two most popular are glass and anti- recordings with antimony electrodes. Whatever the location of the impedance sensors, since the
mony. lon-sensitive eld effect pH electrodes are the type of electrode chosen, each center should esophageal height of re ux episodes is consid-
modi ed eld effect transistors. Clinical stud- preferentially use one device and one type, or a ered one of the advantages of impedance.
ies require a pH sensor that is both affordable limited number of different electrodes.
and reliable. Glass electrodes with an internal Prior to each study, an in vitro two-point cali- Impedance: The Technique. Experience th
reference are "the best," but are expensive and bration must be carried out. The electrode and pH monitoring has shown the pitfalls of an arblr
have a rather large diameter (3.0 to 4.5 mm),!,12 reference are placed in two buffer solutions (usu- trary cutoff limit such as pH 4. A similar com-
Although the passage of such an electrode ally pH l and 7) at either room or body tempera- ated
ment can be made for impedance: the automated
through the nostrils of a baby is, most of the time, ture until stabilization is reached. This calibra- analysisconsiders only a drop ofimpedanevof
technically possible, it does not mean that it is tion should be repeated on returm of the patient 50% or more as a re ux episode. However, it 15
well tolerated and that it is the best option. to rule out electrode failure and to check for slow likely that a drop of 49% also can be uted
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 CHAPTER 50/Esophageal pH and Impedance Measurement 1395

monitoring.'5 Whether acid suppressing medica- GER and speci c symptoms such as bradycardia
tions decrease re ux events or only change the in relation to the presence of acid in the distal
pH of the re ux events has been insuf ciently esophagus. However, provocative testing has the
validated with impedance. This issue is one of the inconvenience that the investigation conditions
priority areas for research with impedance. are unphysiologic, which likely explains discrep-
It is best not to start a pH metry study the same ancies reported in the literature. For instance,
day that an upper gastrointestinal tract endoscopy Ramet and colleagues showed prolongation of
is performed because the sedation, fasting, and the R-R interval on ECGS in infants during pro-
in ated air may be confounders. It is best to start vocative testing with instillation of acid in the
pH metry at least 3 hours after a barium swallow esophagus,30 whereas other investigators could
or radionuclide gastric or esophageal studies. not reproduce these ndings in 24-hour record-
ings under more physiologic conditions.31,32
There is now substantial evidence that both in
PATIENT-RELATED INFLUENCING controls and in majority of infants and children
FACTORS: RECORDING CONDITIONS with classic symptoms of GERD, esophageal
acid exposure is highest during the day, probably
Feeding, position, and physical activity are exam- because of provocation of GER by food ingestion
ples of patient-related factors in uencing re ux and physical activity. Controls have more re ux
events. Patient-related factors that possibly in u-
Figure 1 Rx thorax to show the localization of the pH upright than supine and more re ux awake than
electrode (third vertebra above the diaphragm). A two- ence the results of re ux investigations remain a
asleep.3 The relationship between esophagitis
channel electrode with the distal electrode in the stomach controversial topic.$,15 The answer to the funda-
and nocturnal acid re ux is far from clear.4-36
and the proximal electrode at the third vertebra is shown. mental question regarding whether patient-related Limited experience with impedance con rms
factors should be minimized and standardized is
knowledge for pH monitoring: more re ux dur-
dif cult and necessarilyambiguous. If the re ux ing the day (during activity) than at night (during
to re ux. Although impedance interpretation investigation is performed as part of a diagnostic
sleep), more acid re ux during fasting and more
necessitates a manual analysis, the relevant ques- workup in a patient, it is interesting to undertake
nonacid re ux during feeding.
tion remains what level of decrease in impedance the study during normal daily life. On the other
is needed to be considered as a re ux episode? A
The reproducibility of impedance-pH
hand, if the re ux investigation is performed as
recording on 2 consecutive days is rather poor,
drop in impedance is not related to the volume of part of a clinical research project, recording con- especially for nonacid re ux.32 The variability
the re uxate. The multiple impedance rings allow ditions should be standardized. Standardization
between the number of acid and nonacid re ux
the height of the re ux episode to be identi ed. of recording conditions inevitably causes a loss
episodes with a second recording performed
If pH monitoring is performed with a probe with ofpatient-speci c information. 2 days after a rst recording have a high variation:
multiple pH sensors, it is also possible to deter-
0.2 to 5.3 and 0.04 to 8.6 times the value obtained
mine the height of the re uxate. The major differ- Duration of the Recording
at day 1, respectively.>" However, reproducibil-
ence between both techniques is restricted to the
The duration of the recording should be as close ity of pH monitoring on 2 consecutive days is
detection of nonacid re ux. As a consequence,
as possible to 24 hours and at least 18 hours, reported to have high correlation coef cients,
another fundamental question arises: what is the
including a day and a night period both for pH ranging from 0.88 to 0.98.* Applying a similar
clinical relevance of nonacid or weakly acid and
and impedancemeasurements.,17,18 If pH moni- study design, Nielsen and coworkers reported an
alkaline re ux?
toring is performed for diagnostic purpose, there overall reproducibility of 70% for impedance.39
is no indication for short-duration pH tests (eg, The re ux index at day 2 was 0.2 to 3.3 times the
PATIENT PREPARATION Tuttle and Bernstein tests and 3-hour postpran- initially obtained value at day 1.9
dial recording). The rst reports on the clinical Intraluminal impedance monitoring data can
Other than fasting, no special patient preparation use of pH monitoring concerned esophageal tests be read manually or analyzed automatically using
is required for pH monitoring. The patient should of short duration. Tuttle and Grossman developed commercially available software. Over 95% of
fast for at least 3 to 5 hours before the study, the "standard acid re ux test.»l9 This test was re ux events detected by automatic impedance
depending on the age, to avoid nausea and vom- modi ed by Skinner and Booth° and Kantrowitz pH analysis were con rmed by two independent
iting. If the child is able to communicate, it is and colleagues,"" demonstrating that pH tests can investigators, although they added about 33%
important to reassure the child at the beginning of contribute to de ne abnormal GER. The Tuttle acid, weakly acid, and nonacid re ux episodes.40
the study and explain what will happen. The child test was reported to have a sensitivity of 70%.2 The agreement between investigators for re ux
should understand that the passage of the catheter However, after great initial enthusiasm for this episodes detected by manual reading of 24 hours
through nostrils and pharynx is uncomfortable, test, criticism was overwhelming. The test is impedance-pH tracing was only about 50%.0
but after the rst few swallows, it will feel bet- unphysiologic in requiring intragastric instilla- Interobserver variability was reported much bet-
ter. To facilitate insertion, a spray containing sili- tion of acid and various arti cial maneuvers to ter in impedance recordings obtained in neonates
cone can be placed on the electrode (but not on raise intragastric pressure. In the early 1980s, it during a period of 6 hours. The discrepancy
the pH sensor!) and/or the mucosa of the nostrils was reported that the false-positive rate might be between automatic analysis and manual reading
can be sprayed with a topical anesthetic. Sedation as high as 20% and false-negative rates as high as is in uenced by the preset de nitions of the auto-
should not be used because the sedative interferes 40%.225 Bernstein and Baker demonstrated, in matic reading: the software indicates as acid re ux
with swallowing and in uence LES pressure. 1958, that heartburn could be provoked by infus- only those episodes in which the impedance falls
Histamine, (H,) blockers and proton pump ing diluted hydrochloric acid into the esophagus below 50% of baseline in two consecutive chan-
inhibitors should be stopped at least 3 or 7 days, in susceptible individuals. This test was reported nels simultaneously with a drop in pH below 4.
respectively, before a diagnostic pH monitoring to be 100% positive in heartburn patients.2? A This means that the re ux (or "drop in imped-
(except when the investigation is performed to modi ed Bernstein test was used to illustrate the ance") should reach at least 5 to cm above the
evaluate the acid-blocking effect of the drug). relationship between GER and apnea and stridor pH channel to be detected as "acidic impedance
Antacids are permitted up to 6 hours prior to and between nonspeci c chest pain and GER.2829 re ux." Most pediatric centers choose to register
the start of the recording. Prokinetics should Provocative testing can be used in particular con- all re ux episodes detected with the pH channels
be stopped at least 48 hours before the pH ditions to demonstrate the relationship between independently from the impedance re ux events.
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 1396 PART VI/ Diagnosis of Gastrointestinal Disorders

More data are needed regarding the comparison
between automatic and manual reading. It is clear
that more re ux episodes are detected with man-
ual reading: however, it has not been shown that
more re ux detected equates to better diagnosis.
Moreover, manual reading induces human bias in
the interpretation of the results. In general, "pH-
re ux" does last longer than "impedance-re ux,"
or in other words, acid exposure lasts longer than
bolus exposure. This observation is likely to be
related to a difference in clearance time between
acid and bolus exposure.
Feeding
Feeding during pH monitoring is an area of contro-
versy. On the one hand, it seems logical to forbid
the intake of acidic foods and drinks. However,
many popular foods and beverages have a pH of
<5 (eg, cola drinks, fruit juice, tea, and soup),
resulting in a quite restricted diet. A too restricted
diet might alter the patient's normal dietary habits
in such a way that the investigation is no longer
performed in physiologic conditions. Electrodes
are temperature sensitive; therefore, very hot and
ice cold beverages and foods (eg, coffee, tea, and
ice cream) should be avoided." Chewing gum
or hard candy should be withheld because these
increase saliva production and thereby induce
swallowing and esophageal peristalsis, tending to
normalize test results. This is also true for imped-
ance recording: during periods of increased saliva
production and swallowing, less re ux will occur.
In older children, alcohol intake and smoking
should be recorded on the diary.
In infants, it has been suggested to replace one
or several feedings during pH monitoring with
apple juice.ol This solves the problem of gastric
anacidity after a milk feeding. Apple juice has a
pH of about 4, a very rapid gastric enmptying and
is not part of normal infant feeding. Although the
ingestion of acid, such as a cola drink, might sim-
ulate a re ux episode, the duration of ingestion
is limited to a few minutes and most of the time
irrelevant in relation to 24-hour data. It is also
possible to eliminate these false re ux episodes
with the help of a diary. Impedance (in combina-
tion with pH) recording allows much better deter-
mination of the bolus movement: from proximal
shorten the period of postprandial gastric anacid-
ity, and prolong the periods during which acid
GER can be detected. Combined impedance and
pH recording may enhance understanding of the
effects of various constituents of food on GER.
The impact of postprandial nonacid re ux
decreases with age, since the number of feedings
decreases, and with it the total duration of post-
prandial periods and the overall buffering effect of
milk." It seems logical that nonacid re ux events
decrease with time elapsed from the last meal.*
While symptom corelation (within a 5 minutes
window) is similar between acid and nonacid
re ux (25.2 vs 24.6%), re ux events reaching the
proximal esophagus are more frequently associ-
47
ated with epigastric pain and burping."
Position
Different patterns of GER (upright, supine, and
combined) have been reported in adults and
older children.4 Orenstein and colleagues dem-
onstrated that the prone sleeping position is the
preferred position for infants as far as GER is
concerned because crying time is decreased if
compared with the supine position,6$-67 There
is evidence that the prone anti-Trendelenburg
30° sleeping position reduces GER in normal
subjects and patients, although the position is
dif cult to apply and maintain correctly (infants
have to be tied up in their bed). Meanwhile,
the literature on sudden infant death syndrome
shows that infant mortality decreases if infants
are put to sleep in supine position.°%,6 The posi-
tion of the infant should be recorded on the diary
during re ux monitoring. The impact of position
has been analyzed through combined manom-
etry and impedance in 10 healthy preterm infants
(35 to 37 weeks of postmenstrual age): 89 re ux
episodes were recorded (74% were liquid, 14%
air, and 12% with mixed contents). In the right
lateral position, the total number of re ux epi-
sodes (as well the total as the liquid episodes)
was signi cantly higher than in the left lateral
position despite a faster gastric emptying in the
right position. This nding suggests that the
major pathophysiologic mechanisms causing
o 10
re ux episodes are inappropriate transient relax.
ations of the LES49,50
In addition to position, the effects of formula
feeding and alginate on height, frequency, and
type of re ux have also been studied.Impedance
con rms the ef cacy of an antiregurgitation for-
mula on the frequency and severity ofregurgita-
tion with a trend for a more pronounced effect on
nonacid re ux. Although there was a trend for
re ux to be less proximal, the difference was not
signi cant.5" In other words, with the antiregur-
gitation formula tested, there was no statistically
signi cant difference in the duration andnumber
of acid and nonacid GER, and in the height ofthe
re ux episodes." Impedance shows thatalginates
do not decrease the number of postprandial epi-
sodes of GER, but may marginally decreasethe
height of the re uxate,53
DATA ANALYSIS
Interpretation and Parameters
Interpretation starts with a visual appreciation
of the tracing, which is subjective and dif cult
to standardize (Figure 2). Nevertheless, it is of
the outmost importance to look at the tracing.
A progressive constant reduction in esophageal
pH at the end of a feeding, which continues up
to the next feed, may be suggestive for cow's
milk protein allergy.º Parameters that areclas-
sically analyzed for pH monitoring are the total
number of re ux episodes, the number of re ux
episodes lasting more than 5 minutes, the dura-
tion of the longest re ux episode, and the re ux
index (the percentage of time of the entiredura-
tion of the investigation during which the pH
is less than 4). Fronm all classic parameters, the
acid exposure time or re ux index is the most
relevant. The correlation between all fourparam-
eters is good, and they are closely related to the
re ux index."" Results should also be automati-
cally calculated for periods of interest, suchas
sleep, wakefulness, feeding, postprandial fasting,
and body position. A time relation betweenatypi-
cal manifestations (eg, cough, bradycardia, and
desaturation) and changes in pH (not necessarily

to distal, as happens after a swallow, or from dis-

tal to proximal, as happens during GER.
The in uence of a particular food on the fre-
quency of acid GER episodes detected by pH
monitoring might be opposite to its in uence on
the incidence of re ux episodes: for instance, a pH-1
high fat mneal provokes GER because of delayed
gastric emptying." Since the duration of post-
prandial gastric anacidity after a fat meal is pro-
longed, a meal with a high fat content will result
in delayed gastric emptying and, thus, less acid
re ux episodes will be detected by pH monitor-
ing,2,63 Postprandial GER after feedings varying Event Opdrachter
liggen ete
in fat content is an interesting research topic for symptoom EPS-
1412:00 1/18:00
impedance. Some drugs that in uence gastric emp- 2/00:00 2/08:00

tying have a comparable effect on pH monitoring Figure 2 A 24-hour pH tracing, showing different acid and nonacid re ux episodes, during periods ofwakefulness
and

data: prokinetic drugs enhance gastric emptying, sleep (dark linc). Events (coughing) are cither nonrelated or occur just after a re ux episode.
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 CHAPTER 50/Esophageal pH and Impedance Measurement 1397

a drop in pH below 4) should be searched for. normal ranges should be regarded as a guideline tions measuring re ux during the postprandial
The duration of re ux during sleep has been sug- for interpretation. Reproducibility has been shown period (ultrasound, radiology, and scintigraphy)
gested to be a good selection criterion for re ux for various parameters. Intrasubject reproducibil- are of limited value in the diagnosis of GERD
related to apnea in infancy (the "ZMD-score"),?2 ity supports the diagnostic use of continuous pH because of the high prevalence of GER in the
For unclear reasons, this parameter has been monitoring. In general, a re ux index above 7% postprandial period. The pH of re ux during a
insuf ciently validated. However, it should be is considered as abnormal, a re ux index below postprandial period is mostly above pH 4 (thus
noted that the response time of an antimony elec- 3% as normal, and a re ux index between 3 and regarded as nonacid based on pH-monitoring cri-
trode (the time needed to reach 95% of the exact 7% as indeterminate. However,, normal ranges teria). However, based on experience obtained
pH) is at least 5 seconds. The "area below pH 4" were developed to separate patients at risk for with impedance, there is general consensus that
is a parameter considering the acidity of re ux esophagitis from those not at risk, which is not it is preferable to consider this type of re ux as
episodes,'S which has been shown to correlate the major indication of the procedure. Normal "weakly acid" re ux (Table 3).
better with the presence of re ux esophagitis than ranges proposed by one group can be used by Ifa nasogastric tube passes the cardia, imped-
with the re ux index in children.?4 another group only if the investigations are per- ance shows an increase in postprandial re ux
Various complex re ux scoring systems formed and interpreted in a comparable way. This (from 72 to 122 episodes) in preterm infants.
(Johnson-Demeester Composite Score, Jolley, means that materials and methodology shouid be Del Buono con rmed these ndings in neuro-
Branicki, Kaye, and Boix-Ochoa scoring sys- identical. For some individuals and in some clini- logically impaired children: more than half of the
tems) have been developed. The majority of the cal situations, it may be more important to relate re ux events are nonacidic and would therefore
parameters were developed for assessing re ux "events (eg, coughing, wheezing, and apnea) to go undetected by conventional pH metry.4 The
esophagitis in adults. Jolley and colleagues pro- recorded events rather than to know if the data number of re ux episodes, both acid and non-
posed a score for children. However, there is are within the normal range. There are no normal acid, and the median height of re ux events was
abundant literature, both in adults and in chil- ranges currently available for impedance. increased in the subgroup that was fed through
dren, that not one parameter of pH monitoring Signi cantly fewer acid re ux episodes are a nasogastric tube, compared to the orally fed
(except the "area under pH 4") and no single detected using pH monitoring combined with subgroup.64 However, the difference in GER
symptom has a high speci city for esophagitis. impedance when compared to pH monitoring events may well be explained by the difference
Endoscopy and histology remain the gold stan- alone." Estimates of esophageal acid exposure in neurologic impairment between groups. In a
dard to diagnose esophagitis. In marked contrast using pH monitoring alone were twofold higher small group of seven healthy preterm newborns
to these complex scoring systems is the simple than estimates derived using pH and impedance receiving nasogastric milk feeding, the mean
recommendation by some investigators that the techniques. Of the total acid re ux episodes prevalence of nonacid re ux (29 episodes/24 h)
re ux index or total acid exposure time should be detected by pH monitoring alone, almost three- was more than two times the prevalence of acid
regarded as the most important, if not the only, fourth could not be con rmed by combined pH re ux (12 episodes/24 h) and about 80% of these
variable in clinical practice.1,73 Scores based on and impedance. Detection of signi cant num- re ux episodes reach the proximal esophagus.5
symptom indices are not applicable in infants and bers of "pH only" episodes raises concerns The same group reported in a larger series of
young children. regarding possible overestimations of acid expo- 21 healthy premature neonates a much higher
A major interfering factor in the interpreta- sure that may occur when estimates are based incidence of approximately 70 re ux events in
tion of pH monitoring data is the "yes" or "no" solely on esophageal pH monitoring. 24 hours; of the re ux episodes, 25% were acid,
interpretation provided by computer software: a Weakly Acid Re ux. Weakly acid re ux was 73% weakly acidic, and 2% weakly alkaline,46
pH of 4.01 is regarded as normal, whereas a pH In preterm infants, weakly acidic re ux is more
previously called nonacid re ux. Up to now,
of 3.99 will be considered as acid re ux. Minimal prevalent than acid re ux, particularly during the
there has been general consensus that investiga-
changes in esophageal pH around pH 4 can be at
the origin of different software interpretations,
although without difference in clinical meaning.
The oscillatory index, a parameter measuring Table 3, Number of Re ux Episodes (Total and Weakly Acid) Recorded by Impedance in Children
the time pH oscillates around pH 4, was devel-
No. of No. ofR Ep No. R Ep Weakly Acid
oped to evaluate this risk for erroneous computer
Author (Ref. No.) Indication Children Impedance Imp/Patient R Ep (%)
interpretation.76
A similar commnent can be made regarding Mattioli2 Typical and 50 2,922 S8.4 <l yr: S3
atypical GOR >l yr: 49
impedance: a drop in impedance of 50% is pos-
Peter3 Tube feeding 16 1,152 (esophageal) 72 ?
tulated to be a GER episode. However, it is very 122 9
1,952 (gastric)
unlikely that a drop in impedance of 49, S0, or Del Buono 4 Neurologically 16 425 26.6 56
S1% has a different meaning. Although impedance impaired
allows or more often requires a manual analysis, Lopez Alonso5 Preterm 7 281 40.1 46
the relevant question that remains is: what is the Lopez Alonso6 Preterm 21 1,491 71 73
Condino17 GER disease 34 1,890 55.6 53
decrease in impedance needed to be considered
Condino48 Asthma 24 1,184 197.3 SI
as a re ux episode? The drop in impedance is not
Omar;49 Healthy preterm 10 89 8.9 ?
related to the volume of the re uxate. If pH moni- Corvaglia9 56
Healthy preterm ,055
toring were to be performed with a probe with mul- Wenzl! Regurgitation 14 I,183 84.5 55
tiple pH sensors, it would be possible to determine term infants
also the height of the re uxate. The major differ- Corvaglia? Preterm with s 316 63.2 78
ence between pH and impedance-pH monitoring is regurgitation
Del Buonos3 Effect Gaviscon 20 747 37.3 69
restricted to the detection of weakly acid re ux.
Wenz|and Wenzl55,56 Physiologic apnea 22 364 16.5 89
PeterS7 Pathologic apnea 21 S24 24.9 ?
MousaS Apnea, ALTE 25 1,211 48.4 49
Normal Ranges Rosen59 CRD 28 1,822 65.1 45
As for any measurement, normal ranges are man- Thilmany0 CRD 25 3,235 129,4 ? (Low)
datory. However, because there is a continuum ALTE = apparent life-threatening event.
between physiologic GER and pathologic GERD,
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 1398 PART VI / Diagnosis of Gastrointestinal Disorders

feeding periods.46 In contrast, similar to healthy were studied at a mean age of 26 days (13 to event. In a selected group of 22 adults, a rela-
adults, weakly alkaline re ux was uncommon. 93 days): 2,039 episodes of apnea (median: tion between chronic cough and GER was stud-
Most re ux events are pure liquid during both 67; range: 10 to 346), 188 oxygen desatura- ied by combined manometry and MII-pH.° Using
fasting and during postprandial periods; gas tions (median 6; range O to 25), 44 bradycardias a time frame of 2 minutes and symptom assSo-
re ux is very rare. The majority of re ux events (median 0; range 0 to 24), and 524 episodes of ciation probability, 69.4% of coughingepisodes
in asymptomatic preterms reaches the proximal GER (median 25; range 8 to 62) were detected. were considered independent of a re ux episode.
esophagus or pharynx. The acid exposure related The frequency of apnea in a 20-second period When a "re ux-cough" sequence occurred, the
to re ux events and detected by impedance is before and after an episode of GER was not dif- re ux in 65% of cases was acid, in 29% weakly
signi cantly lower than the total acid exposure ferent than the frequency of apnea not related to a acid, and in 6% weakly alkaline. Contradictions
during 24 hours.'3 Increased acid exposure could re ux-episode [0.19/min (0.00-0.85) vs 0.25/min in the literature on the role of acid and nonacid
be attributable to pH-only re ux events or, less (0.00-1.15)],7 The analysis and conclusions were GER in children with chronic respiratory symp-
frequently, to slow drifts of pH from baselines identical for oxygen desaturations and bradycar- toms may, in part, be explained to the fact that
at approximately 5 to values <<4. These changes dias.> Mousa analyzed the temporal relationship these studies have not considered whether re ux
are not accompanied by a typical impedance pat- between apnea and GER in a group of 25 infants is primary (motility disorder) or secondary (to
tern of re ux but by slow drifts in impedance in presenting with an apparent life-threatening event infection, allergy, respiratory efforts, etc) in
one or two channels. These ndings con rm the or pathologic apnea.A time interval as long as nature.
need for the use of impedance together with pH 5 minutes between apnea and re ux was consid- The use of pH alone for the detection of acid
metry for diagnosis of all GER events. Con- ered acceptable to demonstrate a "temporal link" re ux is very sensitive but lacks speci city com-
versely, Condino and colleagues report in a group between the two phenomena.$$ In total, 527 apnea pared with MIl-pH. pH alone may overdiagnose
of 34 infants, aged between 2 and 11 months, episodes were recorded but only 80 (15.2%) were abnormal acid re ux. Also, the use of pH for
that the distribution or acid and nonacid re ux temporally linked to a re ux episode. Of these the detection of weakly acid re ux has poor
is almost equal: 47% of the re ux episodes were 80 episodes, 37 (7.0% of the total episodes of sensitivity.79
acid and 53% nonacid." apneas) were related to acid re ux and 43 (8.2%)
Chronic respiratory symptoms such as chronic to nonacid re ux. Thus, even when consider-
bronchitis, wheezing, chronic cough, and infant ing a time interval as long as 5 minutes, one can PH MONITORING AND OTHER
apnea have been related to GER. A strong rela- conclude that a relationship between re ux and INVESTIGATIONS
tionship between acid and nonacid GER and respi- apnea is uncommon.> The majority of the re ux
ratory abnormalities was suggested by Wenzl and events reach the proximal esophagus or the phar- Many different techniques to evaluate GER exist,
coleahues: in a group of 22 children presenting ynx, both in asymptomatic preterm babies and focusing on different aspects, such as postprandial
with repetitive regurgitation and chronic respira- in neonates with cardiorespiratory symptoms.6 re ux (scintiscan, barium swallow, and ultraso-
tory symptoms, impedance recorded 364 re ux This lack of discernable differences between nography), histologic abnormalities (endoscopy),
events, of which only 11.4% wereacid.5$Three asymptomatic and diseased infants contravenes continuous measurements that are pH dependent
hundred and twelve (85%) of these re ux epi- the hypothesis for macro- or microaspiration, but (pH monitoring) or not (Bilitec and impedance),
sodes, of which 12% were acid, were associated does not exclude hypersensitivity to re ux as a and pathophysiology by measuring the relax-
with iregular breathing.74 In a minority of these cause for respiratory symptoms. ations of the LES (manometry). Recent evidence
episodes (n = 19), oxygen desaturations of more Chronic respiratory manifestations, such as in adults reveals the clinical utility of Bilitec
than 10% occurred (3/19 or 19% of such episodes coughing and wheezing, are reported to occur in monitoring showing a possible role for duodeno-
were acid). Analysis of the polysomnographic older children with re ux. Rosen and colleagues gastroesophageal re ux in a subset of patients
recording showed 165 episodes of apnea, of reported their experience in 28 children (mean who continue to report re ux symptoms in the
which 30% were associated with a re ux episode; age: 6.5 + 5.6 years) with chronic respiratory setting of normalized esophageal acid exposure
again, the majority (78%) of re ux episodes were disease under treatment with antacid medica- on high-dose proton pump inhibitor. However,
detected with impedance only.* However, an tions. A total of 1,822 episodes of re ux were bile re ux can also be detected by impedance.
association between pathologic central, obstruc- measured with MIl-pH; 45% of them were non- Bilirubin is as toxic to the esophageal mucosa as
tive or mixed apnea and GER has not been con- acid. Multivariate analysis showed a stronger acid, but the number of patients with esophagitis
vincingly demonstrated but has also not yet been association between respiratory symptoms and and only pathologic alkaline or nonacid re ux
well studied. Clear cutoff values discriminating nonacid re ux episodes than with acid re ux epi- and normal acid re ux is small,80,81
normal from pathologic children still need to be sodes. Also the height of the re uxate in the In speci c situations other techniques might be
determined. The number of re ux events per hour esophagus was related to respiratory symptoms: of interest such as lipid laden macrophages, pep-
(two to three events per hour) is slightly lower the higher the re ux, the stronger the associa- sin, and lactose in bronchial secretions. Abnor-
in normal healthy preterm infants than in prema- tion. The association score between symptoms mal pH monitoring does not accurately predict
ture neonates with cardiorespiratory events (four and episodes of re ux detected with imped- the risk for esophagitis.$2,83 In a group of re ux
per hour)."° When compared with pH monitoring, ance and pH monitoring was 35.7+ 28.5 and patients with esophagitis, the sensitivity of pH
impedance is a technique that will allow a more 14.6 ± 18.9 (p = .002), respectively." How- metry is 88% and of scintigraphy is 36%." In a
accurate determination whether apnea of short ever, it is not too surprising that pH monitoring group of patients with abnormal scintigraphy, the
duration is a physiologic phenomenon occurring detects less re ux during antacid treatment. In a sensitivity of pH monitoring is 82%, endoscopy
frequently in relation to an episode of GER.78 series of 25 children (age 6 months to 15 years) 64%, and manometry of the LES 33%. Non-
In a group of 22 infants, 364 episodes of GER with unexplained chronic cough, wheeze, or spu- acid re ux may be inoffensive (simple postpran-
were detected with impedance.4,56 Visual vali- tum production, data support a relation between dial) re ux at a neutral pH, but may also contain
8:
dation records con rmed 165 apneas. Of these acid GER and chronic pulmonary symptoms, but bile, which is toxic for the esophageal mucosa.
events; 49 (30%) were associated with GER and do not support a role of nonacid re ux in chil- There is limited experience with esophageal bile
38 (77.6%) were exclusively recorded by imped- dren with respiratory symptoms not on antacid monitoring in children. The overall correlation
ance.4,30Adecreaseof oxygen saturation >10% medication.60 Condino and colleagues studied between scintiscanning and pH monitoring is
was observed in 19 re ux events recorded with 24 children with recurrent asthma and concluded acceptable (r = .78),6 However, during simul-
impedance, of which only 3 (15.8%) episodes that both acid and nonacid re ux occur with taneous pH recording and scintiscanning, only
were acid (pH <4),4,56 Nineteen preterm infants equal frequency in children with asthma and that 6 of 123 re ux episodes were recorded sin
(gestational age 30 weeks) presenting with apnea most symptoms occur in the absence of a re ux
neously." There is no COTclation the
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 CHAPTER 50 / Esophageal pH and Impedance Measurement 1399

number of re ux episodes detected using scin- treatment is not available. Symptom-correlation sphincter: Can we get closer? Gastroenterology 1987;92:
1357-9.
tigraphy and pH monitoring. Barium studies analysis, especially for extraesophageal symp- 17. Vandenplas Y, Casteels A, Naert M, et al. Abbreviated
seem to have a much lower sensitivity to detect toms, is likely to be more convincing with imped- oesophageal pH monitoring in infants. Eur J Pediatr 1994;
re ux episodes if pH monitoring is regarded as ance than with pH monitoring. 153:80-3.
18. Belli DC, Le Coultre D. Comparison in a same patient of
the gold standard. According to many authors, Since pH monitoring is part of an impedance short-, middle- and long-term pH metry recordings in the
there is a high frequency of both false-positive recording, it is likely that impedance will become presence or absence of gastro-esophageal re ux. Pediatr Res
and false-negative results with barium studies more frequently performed in routine practice.3,94 1989:26:269.
19. Tuttle SG, Grossman MI. Detection of gastroesophageal
that relates to the short investigation time on From the data presented in the chapter, it emerges re ux by simultaneous measurement of intraluminal pres-
the one hand and the intensity of re ux-provok- that it is currently dif cult to draw conclusions sure and pH. Proc Soc Exp Biol Med 1958:98:225-30.
ing maneuvers on the other hand. A 15-minute 20. Skinner DB, Booth DJ. Assessment of distal esophageal
on the precise advantages of the application of
function in patients with hiatal hernia and or gastroesopha-
postprandial period color Doppler ultrasonogra- MIl-pH in children to detect GER events. The geal re ux. Ann Surg 1970;172:627-36.
phy was compared with 24-hour pH monitoring, heterogenicity of the studies (in terms of popu- 21. Kantrowitz PA, Corson JG, Fleischer DJ, Skinner DB.
Measurement ofgastroesophageal re ux. Gastroenterology
showingagreement in 81.5%. However, if pH lations recruited and technical criteria such as
1969;56:666-74.
monitoring was considered the gold standard, the time and symptoms association), and the lack of 22. Kaul B, Petersen H, Grette K, Myrvold HE. Scintigraphy,
speci city of the color Doppler ultrasonography normative data and of outcome measures. More pH measurements, and radiography in the evaluation of
gastroesophageal re ux. Scand J Gastroenterol 1985;20:
was as low as 11%, and there was no correlation homogeneous inclusion criteria and analysis 289-94.
between the incidence of re ux episodes mea- associated with a complete baseline and prospec- 23. Arasu TS. Gastroesophageal re ux in infants and children:
sured with both techniques.$ A far higher num- tive clinical features are mandatory. Impedance is Comparative accuracy of diagnostic methods. J Pediatr
1979;94:663-8.
ber of re ux episodes is detected with impedance a new, promising technical development offering 24. Holloway RH, McCallum RW. New diagnostic techniques
in comparison with pH monitoring because only unexplored possibilities to investigate GER93,94 in esophageal disease. In: Cohen S, Soloway RD, editors.
14.9%of all re uxepisodesareacid. º However, Although many papers suggest a degree of use- Diseases of the Esophagus. New York: Churchill Living-
stone; 1982. p. 75-95.
only 57% of acid re ux episodes are detected fulness, the technique is still in a phase where 25. Richter JE, Castell DO. Gastroesophageal re ux disease:
with impedance.0 the added value to other techniques in the routine Pathogenesis, diagnosis and therapy. Ann Intern Med
work-up of patients needs to be evaluated and 1982:97:93-103.
26. Bernstein IM, Baker IA. A clinical test for esophagitis. Gas-
demonstrated without scienti c rigor. troenterology 1958;34:760-81.
CONCLUSION 27. Benz LJ. A comparison of clinical measurements of gastro-
esophageal re ux. Gastroenterology 1972;62:1-3.
REFERENCES 28. Herbst JJ, Minton SD, Book LS. Gastroesophageal re ux
The miniaturization of devices and electrodes has causing respiratory distress and apnea in newborn infants.
made pH monitoring a procedure that is easy to 1. Vandenplas Y, Koletzko S, Isolauri E, et al. Guidelines for J Pediatr 1979;95:763-8.
the diagnosis andmanagement of cow's milk protein allergy 29. Berezin S. Use of the intraesophageal acid perfusion test
perform, even in the youngest children. Patient-
in infants. Arch Dis Child (in press). in provoking non-speci c chest pain in children. J Pediatr
related factors, such as feeding and physical 2. Nielsen RG, Bindslev-Jensen C, Kruse-Andersen S, Husby 1989;115:709-12.
activity, in uence the results of pH monitoring. S. Severe gastroesophageal re ux disease and cow milk 30. Ramet J, Egreteau L, Curzi-Dascalova L, et al. Cardia, respi-
hypersensitivity in infants and children: Disease associa- ratory and arousal responses to an esophageal acid infusion
Impedance needs further evaluation in children test in near-term infants during active sleep. J Pediatr Gas-
tion and evaluation of a new challenge procedure. J Pediatr
before it can be recommended in clinical prac- Gastroenterol Nutr 2004;39:383-91. troenterol Nutr 1992;15:135 40.
tice. Hardware- and software-related factors, 3. Tuttle SG, Grossman MI. Detection of gastroesophageal 31. Kahn A, Rebuffat E, Sottiaux M, et al. Lack of temporal
re ux by simultaneous measurements of intraluminal pres- relation bctween acid refux in the proximal esophagus and
as well as patient-related factors and recording sure and pH. Proc Soc Exp Biol 1958;98:224. cardiorespiratory events in sleeping infants. Eur J Pediatr
conditions, determine the results of both pH and 4. Miller FA. Uilization of inlying pH probe for evaluation of 1992;151:208-12.
impedance recordings. In clinical practice, pH acid peptic diathesis. Arch Surg 1964;89: 199-203. 32. Suys B, DeWolfD, Hauser B, et al. Bradycardia and gastro-
S. Sifrim D, Castell DO, Dent J, Kahrilas PJ. Gastro-oesoph- esophageal re ux in term and preterm infants: Is there any
monitoring is of interest in a subset of patients in ageal re ux monitoring: Review and consensus report on relation? J Pediatr Gastroenterol Nutr 1994;19;187-90.
whom GERD is suspected but who present with- detection and de nitions of acid, non-acid and gas re ux. 33. Vandenplas Y, DeWolf D, Deneyer M, Sacré L. Incidence
out clear regurgitation or emesis and to measure Gut 2004;53: 1024-31. of gastro-esophageal re ux in sleep, awake, fasted and post-
6. Sifrim D, Dupont I, Blondeau K, et al. Weakly acidic re ux in cibal periods in asymptomatic and symptomatic infants. J
the ef cacy of treatment such as acid suppression patients with chronic unexplained cough during 24 hour pres- Pediatr Gastroenterol Nutr 1988;7:177-81.
and/or prokinetics. Impedance has theoretical sure, pH, and impedance monitoring. Gut 2005;54:449-54. 34. Schindlbeck NE, Heinrich C, König A, et al. Optimal thresh-
bene ts over pH monitoring, but the technique 7. Vandenplas Y, Ashkenazi A, Belli D, et al. A proposition olds, sensitivity, and speci city of long-term pH metry for
for the diagnosis and treatment of gastroesophageal re ux the detection of gastroesophageal re ux disease. Gastroen-
still needs clinical validation. disease in children: A report from a working group on terology 1985:93:85-90.
Impedance is a costly and time-consum- gastroesophageal re ux disease. Eur J Pediatr 1993;1 52: 35. Armstrong D, Emde C, Bumm R, et al. Twenty-four hour
ing technique, which allows for the detection of 704-11 pattern of esophageal motility in asymptomatic volunteers.
8. Vandenplas Y, Belli D, Boige N, et al. A standardized pro- Dig Dis Sci 1990;35: 1 190-7,
all re ux events. The diagnostic sensitivity of tocol for the methodology of esophageal pH monitoring and 36. Avidan B, Sonnenberg A, Schnell TG, Sontag SJ. Acid
MII may correspond to that of the pH probe in interpretation of the data for the diagnosis of gastro-esopha- re ux is a poor predictor for severity of erosive re ux
geal re ux. J Pediatr Gastroenterol Nutr 1992; 14:467-71. esophagitis. Dig Dis Sci 2002;47:2565-73.
untreated patients, but is superior to the pH probe 37. Dalby K, Nielsen RG, Markoew S, et al. Reproducibility of
9. Hirano I. Review article: Modernm technology in the diagno-
In patients treated with antiacid medications." sis of gastroesophageal re ux disease-Bilitec, intralumi- 24-hour combined multiple intraluminal impedance (MII)
Episodes detected only by pH monitoring are nal impedance and Bravo capsule pH monitoring. Aliment and pH measurements in infants and children. Evaluation
Pharmacol Ther 2006;23:12-24. of a new diagnostic procedure for gastroesophageal re ux
numerous in children; therefore, pH monitoring 10. Bothwell M, Phillips J, Bauer S. Upper esophageal pH disease. J Pediatr Gastroenterol Nutr 2006;42:e49(2).
should be included in pH-MIl analyses."Day-to- monitoring of children with the Bravo pH capsule. Laryngo- 38. Vandenplas Y, Helven R, Goyvaerts H, Sacre L. Reproduc-
day variability of the number of nonacid re ux scope 2004;1 14:786-8. ibility of continuous 24 hour oesophageal pH monitoring in
11. Emde C. Basic principles of pH registration. Neth J Med infants and children. Gut 1990;3 1:374-7.
episodes is considerable' and the detection of 39. Nielsen RG, Knuse-Andersen S, Husby S. Low reproduc-
1989;34:S3-9.
nonacid re ux episodes has a high interobserver 12. De Caestecker JS, Heading RC. Esophageal pH monitoring. ibility of 2x 24-hourcontinuousesophagealpH monitoring
variability. Although impedance clearly records Gastroenterol Clin North Am 1990; 19:645-52. in infants and children: A limiting factor for interventional
13. Vandenplas Y, Locb H. Alkaline gastroesophageal re ux in studies. Dig Dis Sci 2003;48: 1495-502
more GER events than pH monitoring, the advan- infants. J Pediatr Gastroenterol Nutr |991:12:448-52. 40. Salvatore S, Hauser B, Luini C, ct al. MIl-pH: What can
tage and the relevance of recording more epi- 14. Vandenplas Y, Badriul H, Verghote M, et al. Glass and we get from the Autoscan and manual readings? J Pediatr
Sodes of GER in daily clinical practice needs to antimony electrodes for oesophageal pH monitoring in dis- Gastroenterol Nutr 2006:42:eS0(1 ).
tressed infants: How different are they? Eur J Gastroenterol 41. Peter CS, Sprodowski N, Ahlbom V, et al. Inter- and intrao-
be demonstrated. Thus, impedance still needs to Hepatol 2004;16:1325-30 bserver agreement for gastroesophageal re ux detection in
De considered as a clinical research tool. The clin- 15. Vandenplas Y. Oesophageal pH Monitoring for infants using multiple intraluminal impedance. Biol Neo-
Gastroesophageal Re ux in Infants and Children. London: nate 2004;85:1 1-4.
Icalrelevance of the detection of weakly acid and J. Wiley & Sons; 1992. 42. Mattioli G, Pini-Prato A, Gentilino V, et al. Esophageal
honacid re ux is also still a matter of research, 16. Cravens E, Lehman G, O'Connor K, et al. Placement of impedancepH monitoring in pediatric patients: Preliminary
Decausecurrent data are inconclusive and speci c esophageal pH probes 5 cm above the lower esophageal experience with 50 cases. Dig Dis Sci 2006;51:2341-
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