J Clin Gastroenterol 2003;37(1):14–22.
© 2003 Lippincott Williams & Wilkins, Inc.
Clinical Review
Esophageal and Gastric Diseases
Ambulatory 24-hour Esophageal pH Monitoring
Why, When, and What to Do
Christopher G. Streets, MRCS, and Tom R. DeMeester, MD
reasons: (1) the technique measures and quantifies the basic
pathophysiologic problem of GERD, namely the exposure
time of the distal esophagus to excessive gastric juice; (2)
the measurement is quantitatively related to the degree of
esophageal mucosal injury; and (3) the episodes of gastric
juice exposure can be correlated with the patient symptoms.
This article discusses why ambulatory 24-hour esophageal pH monitoring has become the “gold standard” for the
diagnosis of GERD, how to interpret the results using a
variety of pH end points, how to perform the study, and the
technical modifications that are being made to improve the
test.
Abstract
The incidence of gastroesophageal reflux disease (GERD) is increasing and if left untreated can lead to significant patient morbidity and even death. The disease results from the abnormal reflux
of gastric contents into the distal esophagus causing symptoms in
most and subsequent mucosal damage in some. Several investigations can be used to confirm the diagnosis, but most are dependent
on the presence of sequelae and complications of the disease. The
physiologic test of ambulatory 24-hour esophageal pH monitoring
has proved to be the most sensitive and specific diagnostic investigation. It measures increased esophageal exposure to gastric juice
by detecting the concentration of hydrogen ions (pH <4) in the
distal esophagus. The technique measures gastric juice exposure at
a point 5 cm above the manometrically determined upper border of
the lower esophageal sphincter. The exposure is measured in components of frequency of reflux episodes, duration of reflux episodes, and accumulated exposure time. The components are integrated into a composite score, which is reproducible, gender and
race independent, and correlates with the degree of esophageal
epithelial damage determined histologically. The composite score
has been shown to be the most reliable measurement of a therapeutic acid suppression regimen or an effective antireflux operation.
t is estimated that up to 11% of the US population experience heartburn daily and 30% every 3 days.1 Despite
such reports the true prevalence of gastroesophageal reflux
disease (GERD) within society is difficult to determine because the disease can also cause a variety of atypical symptoms. Further, it is questionable whether individuals who
experience heartburn every 3 days have the disease. Consequently, a number of tests are used by the physician to
identify individuals who truly have GERD. These include
barium swallow, upper gastrointestinal endoscopy, acidperfusion test, and ambulatory 24-hour esophageal pH
monitoring.2 Of these, ambulatory 24-hour esophageal pH
monitoring has grown in popularity. This has occurred for 3
DEFINING GASTROESOPHAGEAL
REFLUX DISEASE
In clinical practice it is important to have an accurate
definition of a condition before setting out to investigate and
diagnose it. Unfortunately, over time, the lack of a universally accepted definition for GERD has hindered its investigation and confused the literature. Some investigators
have used symptoms to define GERD, while others have
concentrated on the presence of its complications, such as
endoscopic esophagitis. Defining the pathologic process of
gastroesophageal reflux using symptoms or complications is
fraught with problems, as will be highlighted in the following section. A more sound definition would consider the
pathophysiologic abnormality at play, and thus the definition of GERD adopted by the authors is “the abnormal
exposure of the esophagus to gastric juice regardless of
symptoms or complications.” In most patients gastric juice
contains hydrogen ions that can be used as a marker for the
reflux of acid gastric juice into the esophagus. The presence
of hydrogen ions are detected by monitoring the esophageal
luminal pH over a 24-hour period.
From the Department of Surgery, Keck School of Medicine, University
of Southern California, Los Angeles, California.
Address correspondence and reprint requests to Dr. Tom R. DeMeester,
Chairman of Surgery, Department of Surgery, Keck School of Medicine,
University of Southern California, 1510 San Pablo Street, Suite 514, Los
Angeles CA. E-mail: demeester@surgery.usc.edu.
WHY ESOPHAGEAL PH MONITORING IS THE
GOLD STANDARD FOR THE DIAGNOSIS OF
GASTROESOPHAGEAL REFLUX DISEASE
The symptoms experienced by individuals considered to
have GERD are numerous and varied. Typical symptoms
I
14
C.G. Streets and R.R. DeMeester
15
Ambulatory Esophageal pH Monitoring
consist of heartburn and regurgitation, while atypical symptoms include hoarseness, wheezing, cough, and chest pain.
Although exposing the esophageal mucosa to acidic gastric
juice will cause one or more of these symptoms in most
patients, reliance solely upon symptoms as an indication of
increased esophageal exposure to gastric juice is inaccurate.
In the absence of endoscopic esophagitis, there are many
other disorders that can cause similar symptoms. These include diffuse esophageal spasm, achalasia, esophageal carcinoma, peptic ulcer disease, pyloric stenosis, cholelithiasis,
and coronary artery disease. It also needs to be appreciated
that reflux disease may include elements of duodenogastric
reflux and esophagopharyngeal reflux. The symptoms of
duodenogastric reflux are more gastric in character and include epigastric pain, nausea, vomiting, postprandial fullness, and belching. Symptoms of the esophagopharyngeal
reflux are more respiratory in character, and include choking, chronic cough, wheezing, and hoarseness. In an individual with reflux disease, these atypical symptoms may be
present to such a degree that they mask the typical symptoms of heartburn or regurgitation. Making a diagnosis of
increased esophageal acid exposure based only on the presence of typical symptoms can overlook disease in a considerable number of patients. Indeed, the sensitivity (ie, the
ability to detect GERD when it is known to be present) of
the typical symptom heartburn is 68% and its specificity (ie,
the ability to exclude GERD when it is known to be absent)
is 63%.3 Making the diagnosis of increased esophageal acid
exposure based on the presence of atypical symptoms is
even more problematic. Consequently, atypical symptoms
should be investigated as a possible manifestation of reflux
disease and typical symptoms should be investigated if patients fail to respond to therapy or if invasive therapy is
planned, because no one symptom complex is all inclusive
for the diagnosis of GERD. It is important to appreciate that
many patients with atypical symptoms may have functional
dyspepsia and GERD is not the diagnosis. Further, relying
solely on atypical symptoms as an indicator for increased
esophageal acid exposure can encourage the inappropriate
and nonspecific use of acid suppression therapy; an example
is the knee-jerk prescription of proton pump inhibitors in
patients with persistent symptoms after antireflux surgery,
76% of whom have been shown to have normal esophageal
acid exposure.4
Persistent esophageal exposure to gastric juice does not
cause mucosal injury, such as ulceration, esophagitis, stricture and Barrett metaplasia in all individuals.5 Consequently, it is not possible to define the disease by the
presence of mucosal injury. Endoscopy, while able to identifying mucosal injury caused by the disease, may lead to
the false conclusions that those patients without mucosal
injury do not have GERD. Since about half of the patients
with symptoms of GERD will not have gross mucosal injury, endoscopy has a diagnostic sensitivity of 62%. Muco-
sal injury, when present however, is a reliable sign of
increased esophageal exposure to gastric juice and has a
specificity of 96%.6 On rare occasions esophagitis may be
caused by unrecognized drug induced chemical injury.
Experience with other diagnostic tests for GERD have
been disappointing. A barium esophagogram rarely demonstrates the reflux of barium from the stomach into the
esophagus. Rather, it focuses on the anatomic alterations
associated with the disease such as hiatal hernia, Schatzki
ring or stricture. Consequently it has a diagnostic sensitivity
of 40% and a specificity of 85%.7 The Bernstein test, in
which 0.1N hydrochloric acid is infused alternately with
normal saline into the esophagus while asking the patient to
report their symptoms, has a sensitivity of 84% and a specificity of 83%. Its real value is in measuring the sensitivity of
the esophagus to acid gastric juice.7 In contrast, 24-hour
esophageal pH monitoring has the highest sensitivity and
specificity for GERD, both 96% (Table 1). The reason is
that other tests infer the presence of acid in the esophagus,
and are thus liable to error, whereas 24-hour esophageal pH
monitoring actually measures the amount of esophageal exposure to gastric juice.6
The American Gastroenterological Association has recognized the importance of documenting the presence of
GERD and recommends the use of ambulatory esophageal
pH monitoring to (1) document abnormal esophageal acid
exposure in an endoscopy-normal patient who is being considered for antireflux surgery; (2) evaluate patients after
antireflux surgery who are suspected to have ongoing abnormal reflux; (3) evaluate patients with either normal or
equivocal endoscopic findings or reflux symptoms that are
refractory to proton pump inhibitor (PPI) therapy; (4) detect
reflux in patients with chest pain after a normal cardiac
evaluation; (5) evaluate a patient with suspected otolaryngologic manifestations (laryngitis, pharyngitis, chronic
cough) of GERD; and (6) document concomitant GERD in
an adult onset, non-allergenic asthmatic suspected of having
reflux-induced asthma.8 Recently the measurement of effectiveness of acid suppression therapy has emerged as a
further indication for 24-hour esophageal pH monitoring. It
has been shown that inadequate medical therapy, while effective in controlling symptoms may allow continued reflux
with microscopic injury to the esophageal mucosa.9
Experience with 24-hour esophageal pH monitoring has
shown that there are several reasons for increased esophaTABLE 1. Diagnostic tests for gastroesophageal
reflux disease.
Test
Barium esophagogram
Upper gastrointestinal endoscopy
Bernstein test
Ambulatory 24-hour esophageal monitoring
Sensitivity
Specificity
40
68
84
96
85
96
83
96
16
geal acid exposure, all of which can, but not always give
rise to symptoms of gastroesophageal reflux disease. They
are: (1) over-distension of the stomach from swallowed air
or gluttony resulting in transient loss of the lower esophageal sphincter (LES) barrier, (2) persistent loss of the LES
barrier, (3) ineffective esophageal clearance of physiological reflux due to poor esophageal body motility and/or reduced saliva production, (4) gastric acid hypersecretion, and
(5) delayed gastric emptying secondary to neuromuscular
disease or outflow obstruction.
HOW TO INTERPRET ESOPHAGEAL PH
MONITORING—THE COMPOSITE SCORE
Continuous esophageal pH monitoring has been available since the early 1960s,10 but the work of Johnson and
DeMeester11 in the 1970s simplified the procedure and provided a method of interpreting the data obtained. The probe
measures and records continuously the esophageal pH 5 cm
above the upper border of the LES during a 24-hour period.
Precise location of the pH probe is important since the lower
or higher it is placed in the esophagus, the more or less
physiologic esophageal acid exposure will be recorded.
Consequently, normal values for acid exposure vary with
the location of the probe. Further, placing the probe at 5 cm
allows for the upward movement of the LES on swallowing
without the threat of having the probe dip into the acidic
environment of the stomach.
Of particular interest in analyzing the 24-hour pH record
is the time the esophageal pH is less than 4. This cut-off was
chosen for a number of reasons: (1) at pH 4 normal subjects
first begin to experience the symptom of heartburn;12 (2) the
digestive enzyme pepsin, a key contributor to esophagitis, is
activated at a pH of less than 4;13 (3) in normal subjects,
without GERD, the esophageal pH is greater than 4 for a
median of 98.5% of the 24-hour monitored period.14 Consequently, measuring the time the esophagus is exposed to
pH less than 4 over a 24-hour period enables (1) quantitation of the time the esophageal mucosa is exposed to gastric
juice, and how and when that exposure occurs (ie, in several
long episodes or many short episodes; during the day, after
meals or when asleep, (2) quantitation of the time it takes
for the esophagus to clear refluxed acid, and (3) correlation
of esophageal acid exposure with the patient’s symptoms.15
A 24-hour period is necessary so that measurements are
made over 1 complete circadian cycle, and allows for determining the effect of physical activity and body position
on esophageal acid exposure, such as running, lifting, bending, etc.16
At the authors’ institution, all ambulatory pH studies are
carried out over a 24-hour period. This typically provides
20 to 22 hours of interpretable data. Other investigators
have reported that shorter periods of recording yield similar results. In 1985, Walther and DeMeester showed that an
8-hour study, equally divided into upright and supine posi-
J Clin Gastroenterol, Vol 37, No. 1, 2003
tions was an excellent predictor of the 24-hour pH score.17
More recently, Dobhan and Castell demonstrated that a 16hour overnight pH recording (4.00 PM to 8.00 AM) provided a reliable measurement of 24-hour esophageal acid
exposure.18
Using the single measurement of the percent time the
esophageal pH is below 4 during the 24-hour period, although concise, does not reflect how the exposure occurred
(ie, in a few, long episodes or in several short episodes).
This aspect is important, as the effect of a single long episode on the esophageal mucosa can be more significant than
several short episodes. This is analogous to rapidly passing
one’s hand in and out of the flame of a candle without pain,
in contrast to leaving the hand in the flame for an equivalent
but continuous period. The latter is likely to produce a serious burn. Consequently, to quantitate esophageal acid exposure more completely, 2 additional assessments are
necessary: the frequency of the reflux episodes and their
duration. Therefore, to provide a holistic measurement of
esophageal acid exposure the following units are used:
1. The cumulative time the esophageal pH is below 4 expressed as a percentage of the total, upright and supine
time;
2. The frequency of the reflux episodes expressed as the
number of episodes per 24 hours; and
3. The duration of the episodes expressed as the number of
episodes greater than 5 minutes per 24 hours and the time
in minutes of the longest episode recorded.
In some situations it can be helpful to know the time that
the esophageal pH is above 6, 7, and 8 to quantitate the
alkaline exposure. In this situation there cannot be absolute confidence that an increase in alkaline exposure is due
to the reflux of gastric juice with a high pH, although this
is the most common cause. Other causes for increased
alkaline exposure are increased saliva secretion, oral bacterial contamination from diseased teeth and gums, or pooling
of contaminated saliva in an obstructed esophagus.19 Drift
and calibration error of an antimony probe may also be
responsible.20
Normal values for the 6 components of the 24-hour test
above and below various whole number pH thresholds were
originally derived from 50 asymptomatic control subjects
and are shown in Table 2. The upper limits of normal were
established at the 95th percentile. Figure 1 shows the median and the 95th percentile of the normal values for each
component, with patient values denoted by the shaded area.
If the value of a symptomatic patient is outside the 95th
percentile of normal subjects for the pH threshold selected,
he or she is considered abnormal for the component measured. Experience using the threshold of pH 4 has shown a
remarkable uniformity in the normal values of the 6 components from centers around the world, indicating that
C.G. Streets and R.R. DeMeester
17
Ambulatory Esophageal pH Monitoring
TABLE 2. Values for each of the six components of the 24-hour esophageal pH Composite Score at various pH
thresholds in normal individuals (n = 50).
pH <1
% total time
% upright time
% supine time
No. of episodes
No. of episodes >5
Longest episode
pH <2
% total time
% upright time
% supine time
No. of episodes
No. of episodes >5
Longest episode
pH <3
% total time
% upright time
% supine time
No. of episodes
No. of episodes >5
Longest episode
pH <4
% total time
% upright time
% supine time
No. of episodes
No. of episodes >5
Longest episode
pH <5
% total time
% upright time
% supine time
No. of episodes
No. of episodes >5
Longest episode
pH <6
% total time
% upright time
% supine time
No. of episodes
No. of episodes >5
Longest episode
pH <7
% total time
% upright time
% supine time
No. of episodes
No. of episodes >5
Longest episode
pH >7
% total time
% upright time
% supine time
No. of spisodes
No. of episodes >5
Longest episode
pH >8
% total time
% upright time
% supine time
No. of episodes
No. of episodes >5
Longest episode
min.
min.
min.
min
min.
min.
min
min.
min.
Mean
Std dev
Med
Min
0.01
0.04
0
0.80
0
0.11
0.05
0.13
0
2.46
0
0.41
0
0
0
0
0
0
0
0
0
0
0
0
0.30
0.80
0
12.00
0
2.00
0.10
0.35
0
8.25
0
1.29
0.25
0.69
0
11.73
0
2
0.17
0.31
0.04
5.24
0.04
1.12
0.41
0.84
0.15
6.18
0.20
3.47
0
0.10
0
3.50
0
0.10
0
0
0
0
0
0
2.20
5.30
0.90
27.00
1.00
24.00
1.32
2.05
0.35
19.90
0.45
4.07
2.06
4.56
0.76
25.35
1.00
18.78
0.64
1.07
0.21
11.90
0.38
3.22
0.77
1.39
0.47
8.65
0.83
5.11
0.40
0.50
0
10.50
0
1.40
0
0
0
0
0
0
3.40
6.70
2.70
38.00
5.00
33.00
2.79
4.59
1.19
29.6
1.45
9.90
3.26
6.32
2.32
36.90
4.18
26.95
1.51
2.34
0.63
19.00
0.84
6.74
1.36
2.34
1.00
12.76
1.18
7.85
1.15
1.60
0.10
16.00
0
4.00
0
0
0
2.00
0
0
6.00
9.30
4.00
56.00
5.00
46.00
4.45
8.42
3.45
46.9
3.45
19.8
5.89
9.16
3.86
53.80
4.73
39.40
9.39
4.72
13.63
44.58
5.22
34.09
9.82
4.30
18.77
32.57
5.34
40.56
5.10
3.60
3.56
37.50
3.00
19.95
0.30
0.10
0
5.00
0
1.50
41.90
16.00
68.60
142.00
18.00
202.10
31.96
15.10
54.79
125.15
16.90
128.95
39.45
15.92
64.83
138.43
18.00
189.70
47.61
22.84
75.50
85.10
11.82
334.57
17.55
17.72
24.53
42.96
5.58
177.52
47.05
17.70
84.10
83.00
11.00
325.75
8.30
1.60
7.10
21.00
3.00
22.6
83.00
63.50
99.90
243.00
27.00
679.00
76.48
60.76
99.58
173.60
21.90
626.40
81.74
63.17
99.87
231.18
25.90
666.35
94.92
92.56
97.52
59.72
10.76
757.55
7.52
8.31
9.15
56.11
7.63
271.68
97.75
95.75
100.00
45.00
8.50
737.95
54.30
69.80
39.80
2.00
1.00
131.10
100.00
100.00
100.00
240.00
37.00
1459.00
99.95
100.00
100.00
184.45
23.90
1338.30
100.00
100.00
100.00
227.90
33.70
1458.2
5.08
7.44
2.48
8.38
3.72
24.00
7.52
8.31
9.15
7.87
8.63
26.70
2.25
4.25
0
5.55
2.00
11.55
0
0
0
0
0
0
45.70
30.20
60.20
38.00
59.00
103.70
16.54
28.57
16.09
27.00
13.80
87.77
38.03
30.01
49.92
34.98
47.18
99.41
0.03
0.05
0
1.30
0.02
0.48
0.12
0.18
0
4.86
0.14
1.93
0
0
0
0
0
0
0.80
1.20
0
33.00
1.00
10.4
0.15
0.30
0
6.70
0
5.04
0.64
0.95
0
26.68
0.73
10.02
esophageal acid exposure is similar among normal subjects
despite variations in nationality and dietary habit.
The first analysis of 24-hour esophageal pH records obtained from patients with typical symptoms of gastroesophageal reflux showed that not all of the 6 parameters
0
0
0
0
0
0
Max
95%
97.5%
measured were always abnormal. The component most
commonly abnormal was acid exposure during the recumbent period whereas the total number of reflux episodes per
24 hours had the lowest incidence of abnormality. This
observation indicated a need to define when the 24-hour pH
18
J Clin Gastroenterol, Vol 37, No. 1, 2003
FIGURE 1. Graphic display of the
6 components of esophageal pH
exposure showing the median and
95th percentile levels in 50 normal
individuals with whole pH values
above and below 6.0 as thresholds. The shaded area represents
measurements made in a patient.
When the shaded area exceeds
the 95th percentile line for a given
pH threshold, the patient is considered to have an abnormal value for
the component measured. A: Percent cumulative exposure for total
time. B: Percent cumulative exposure for upright time. C: Percent
cumulative exposure for supine
time. D: Number of episodes. E:
Number of episodes lasting longer
than 5 minutes. F: Length of longest reflux episode.
record was abnormal. Even though the 6 components measured provided a means for quantitating gastric juice exposure, the observation that some were abnormal while others
at the same time were normal, made it unclear when an
individual should be considered to have increased exposure
to gastric juice. To solve this problem, the standard deviation of the mean of each of the 6 components measured in
50 normal subjects was used as a weighing factor (Table 3,
pH <4). To use standard deviation in this manner it was
necessary to deal with the data as though they were parametric. Therefore, an artificial zero point was established 2
TABLE 3. Normal values for esophageal exposure to
pH <4 (n = 50).
Component
Mean
SD
95%
Total time
Upright time
Supine time
No. of episodes
No. >5 min
Longest episode
1.51
2.34
0.63
19.00
0.84
6.74
1.36
2.34
1.0
12.76
1.18
7.85
4.45
8.42
3.45
46.9
3.45
19.8
C.G. Streets and R.R. DeMeester
standard deviations below the mean value measured in the
50 normal subjects for each particular component even
though in some situations this would be below 0 and practically an impossibility, (ie, no individual could have less
than 0 reflux. Nevertheless, this allowed a scoring system to
be built around the standard deviation as a weighting unit,
while treating the data as if they had a normal distribution.
Thus, any measured value from a patient could be referenced to this artificial 0 point and, in turn, be awarded
points based on dividing the measured value by the standard
deviation of the mean of the normal value for the specific
component (Fig. 2). The formula used to perform this calculation was:
Patient’s value ⳯
19
Ambulatory Esophageal pH Monitoring
冉
mean − SD
1
+1−
SD
SD
冊
Mathematical reorganization of this formula gave a simpler
version:
Component score =
Patient value − mean
+2
SD
The use of the constant 2 is not essential since it altered the
magnitude of the score by the same value in every case.
However, in practice a constant is used for the convenience
of maintaining a positive value when scoring each component. The minimum value of that constant is 1 scoring unit.
So the simplified formula for scoring each component in
practice is:
Component score =
Patient value − mean
+1
Standard deviation
Using the standard deviation of the mean of the normal
value for each component weighs each measured component of the 24-hour pH patient’s record according to the
dependability and reliability of the measurement. For example, in normal subjects the number of reflux episodes per
24 hours had a very wide standard deviation, resulting in a
large number used to weigh the measured value in patients.
This rewarded few points for this particular component. In
contrast, normal individuals rarely reflux at night. Therefore, the standard deviation for supine reflux is small and
consequently, nocturnal acid exposure results in more
points or greater weight than other components. A 24-hour
pH composite score was obtained by adding the points calculated for each of the 6 components. The upper limit of
normal (95th percentile) for the composite score for each
whole number pH threshold is shown in Table 4. Comparison of 24-hour pH data from normal subjects from 3 institutions using the pH threshold of less than 4, showed great
uniformity and confirmed that the amount of esophageal
acid exposure in normal individuals could be quantitated
and used to develop diagnostic threshold values.21
Recently the process of reading the pH record has been
computerized and the amount of esophageal acid exposure
at each whole number pH threshold has been measured. The
data are expressed as the percentage time the esophageal pH
is below 1, 2, 3, 4, 5, 6 or 7, or above 7 or 8. The number
of reflux episodes, the number of episodes lasting longer
TABLE 4. Distribution of composite scores at various pH
thresholds in normal individuals (n = 50).
FIGURE 2. Concept of using the standard deviation as the
scoring unit to score the component of the percent time that
pH was less than 4 for the total period. Note the establishment of an abstract zero point 2 standard deviations below
the mean value for total-period of exposure below pH4 measured in 50 normal subjects. Theoretically, this allows scoring
the measurement in patients as though the normal values
were parametric. In this example the patient’s total acid exposure below pH 4 is of 4.8% and has a score of 4.41.
PH
Mean
Std Dev
Med
Min
Max
95%
97.5%
<1
<2
<3
<4
<5
<6
<7
>7
>8
4.06
6.03
6.01
5.95
6.00
6.00
6.00
6.00
4.94
3.54
4.35
3.99
4.43
4.69
4.23
2.32
4.55
3.90
2.90
4.65
4.75
4.95
4.85
5.95
6.30
4.50
3.80
2.90
3.60
1.50
0.40
0.50
−3.00
−7.40
1.80
3.80
22.40
25.80
16.20
18.00
16.60
15.20
9.00
25.60
29.90
14.20
17.37
14.10
14.72
15.76
12.76
8.55
14.90
8.50
17.80
25.09
15.93
17.64
16.49
14.65
8.89
22.69
9.60
20
FIGURE 3. Graphic display of the composite score used to
express the overall result of a 24-hour esophageal pH recording. The lower line represents the median score and the
upper line the 95th percentile of 50 normal subjects. The
black area represents the composite score of the patient, with
increased esophageal acid exposure measured at pH <4.
than 5 minutes and the longest reflux episode are also measured for each pH threshold. The data for each component
are shown graphically in Figure 1 as previously mentioned.
A composite score calculated from all the components for
each pH threshold can also be expressed graphically (Fig. 3).
In 1992, Jamieson et al14 evaluated the sensitivity, specificity, and reproducibility of each of the individual components and the final composite score of 24-hour pH
monitoring to diagnose GERD. Using receiver operating
curves to compare the true-positive and false-positive rates,
the composite score and percent total time pH <4 were
shown to be the best discriminators of normal from abnormal, with the composite score slightly better than percent
total time pH <4. The study also verified that while percent
total time pH <4 was greater in males than in females, the
final composite score did not vary with gender. This obviated the need for separate gender-based normal values. It
also showed that the setting in which the 24-hour esophageal pH monitoring was performed, in-patient or ambulatory, did not affect the accuracy and reproducibility of the
results. This was true in so far as patients could be accurately identified as being normal or abnormal. However, the
degree of abnormal exposure was related to the degree of
patient activity.
J Clin Gastroenterol, Vol 37, No. 1, 2003
For many years, pathologists believed that the only diagnostic criterion for esophagitis was inflammation; however, in 1970, Ismail-Beigi et al22 observed that some
patients with clinical symptoms suggestive of reflux had
normal or minimal endoscopic abnormalities. These patients on biopsy had hyperplasia of the esophageal squamous epithelium, a finding which they postulated reflected
an early histologic manifestation of acid-induced injury.
Hyperplasia was defined as being present when the length
of the subepithelial papillae of the lamina propria and the
width of the basal zone exceeded more than 67% and 15%
of the thickness of the mucosa respectfully. Subsequent
studies confirmed these observations. Johnson et al23 demonstrated that exposure of the distal esophageal mucosa to
acid gastric juice as quantified by 24-hour esophageal pH
monitoring could be related to these morphologic findings.
The degree of esophageal acid exposure correlated directly
with increases in both relative and absolute length of the
subepithelial papillae and also to relative basal zone hyperplasia. This relationship was supported by the observation
that both papillary length and width of basal zone hyperplasia decreased after antireflux surgery returned the esophageal acid exposure to normal levels.
Oberg et al24 performed 24-hour esophageal pH monitoring in patients with and without cardiac mucosa at the
gastroesophageal junction. Those with cardiac mucosa had
significantly increased esophageal acid exposure as well as
other hallmarks of reflux disease, such as a hiatal hernia and
defective LES. In 96% of patients the cardiac mucosa was
also found to have an inflammatory infiltrate. They concluded that the formation of cardiac mucosa represented the
earliest histologic signs of gastroesophageal reflux. In a
subsequent publication, this same group observed that in
patients with Barrett esophagus, the length of the intestinalized cardiac mucosa correlated with the degree of distal
esophageal acid exposure determined by ambulatory 24hour pH monitoring.25
Recently, Campos et al used multivariate analysis to determine the strongest preoperative factors predictive of a
favorable outcome after uncomplicated laparoscopic Nissen
fundoplications.26 Of all the variables considered, there
were 3 that significantly predicted a successful outcome –
an abnormal 24-hour pH composite score, a typical primary
symptom (heartburn or regurgitation), and symptomatic improvement in response to acid suppression therapy. If all 3
of these factors were present, a good or excellent outcome
from anti-reflux surgery was obtained in 97.4% of cases.
Further analysis of the data showed that only 75% of patients with typical symptoms that responded to acid suppression therapy, but a normal composite score had a good
or excellent outcome. Of the 3 variables, an abnormal composite score was the strongest predictor of success and so
emphasizes the importance of 24-hour esophageal pH monitoring in preoperative assessment of patients with GERD.
C.G. Streets and R.R. DeMeester
Ambulatory Esophageal pH Monitoring
PERFORMING THE TEST
Twenty-four hour esophageal pH monitoring is usually
initiated in the esophageal function laboratory where the pH
probe is properly positioned and the patient is outfitted with
the monitoring equipment. Prior to the test, the patients
must abstain from medication known to affect gastroesophageal motility and gastric acid production (7 days for
PPIs, 72 hours for prokinetics, 24 hours for H2 receptor
antagonists, and 24 hours for antacids), and take nothing by
mouth the night before the study. Written informed consent
is obtained and the patient has a nostril anaesthetized with
topical 2% lidocaine or 4% cocaine administered with a
Q-Tip. At the authors’ institution, transnasal esophageal
manometry is performed to accurately locate the upper border of the LES before each pH study. The manometry catheter is removed and a multi-use glass or a single-use
antimony monocrystalline pH catheter is introduced. If
there is an interest in monitoring at the alkaline pH thresholds of 7 or 8, a glass probe should be used since it is known
that an antimony probe does not provide an accurate measurement of hydrogen ion concentration at pH values
greater than 4.20
The probe is calibrated in buffered solutions of pH 7.0,
4.0 and 1.0 prior to insertion. The probe is passed initially
into the stomach to confirm that acid is present and that the
probe has not coiled in the esophagus. It is then withdrawn
until the tip comes to lie at a point 5 cm above the upper
border of the LES. The catheter is taped securely to the
nose, run over and behind the ear, and connected to a portable digital data recorder worn around the patient’s waist.
The patient is instructed to have an active day and remain
in the upright or sitting position until retiring to bed in the
evening. Also, they are instructed not to eat or drink between their meals, chew gum or smoke. One meal is standardized consisting of a hamburger, fries and milkshake,
obtained at McDonalds or Burger King. The other meals
consist only of food with a pH between 5 and 7; a list of
suitable items is provided to the patients. Each meal must be
eaten at 1 sitting and accompanied by only water, milk,
coffee or tea. Carbonated beverages, alcohol and fruit drinks
are to be avoided. The patient is instructed to lie flat at night
with, if possible, only a single pillow and no blocks under
the head of the bed. No medication affecting gastrointestinal
function is to be taken during the monitored period. A diary
of events is kept and includes the beginning and end of
mealtimes, the time when the patient went to bed and got up
in the morning, and the time and nature of any symptoms
experienced.
On returning to the esophageal function laboratory the
next day, the probe is removed, placed in the 3 buffer solutions to check its calibration and the recorded data transferred to a PC for analysis with a commercial software
program. This produces a summary report detailing the vari-
21
ous component values and the calculated composite score
for the patient. A postprandial acid exposure is also calculated by measuring the percentage time that the pH is less
than 4 during the 2-hour postprandial periods following the
standardized meal.27
A NOVEL TECHNIQUE FOR MONITORING
ESOPHAGEAL PH
The conventional method for measuring esophageal pH
consists of a pH electrode located at the end of a long
indwelling catheter that passes up the esophagus, along the
posterior wall of the pharynx and out the nose. The catheter
is uncomfortable and socially embarrassing. Consequently,
despite patients being encouraged to pursue their normal
everyday
activities during the monitoring period, Fass et
28
al have shown that the study significantly reduces refluxprovoking activities. Many patients experienced side effects, such as throat discomfort and runny nose, and felt
uncomfortable most of the monitored period. Several, despite encouragement to do otherwise, spent an atypically
sedentary day when monitored.
To increase the comfort and acceptability of this important
diagnostic test, a number of investigators have used radiotelemetric pH monitoring systems.29,30 However, the ability of
these early systems to become incorporated into routine clinical practice has been thwarted by a number of problems including electrode drift, battery life, poor signal reception and
general unreliability. These systems also required a thread
to suspend the radiotelemetric pH capsule at the correct level
in the esophagus. The proximal end of the thread was brought
out through the mouth and attached to the subject’s cheek. This
still caused some oropharyngeal discomfort.
Recently a “clip-on” and truly catheter-free radiotelemetric pH capsule, called the BRAVO™ pH monitoring system
(Medtronic Inc., Shoreview, MN), has been developed and
is currently used at several institutions. The system consists
of a small monocrystalline antimony pH sensor that is delivered transnasally and attached to the esophageal mucosa
at a point 5 cm above the previously manometrically determined proximal border of the LES. The delivery catheter is
then removed. The pH data is transmitted to a remote receiver worn on the patients’ belt. Early experiences indicate
that this new technique is not only comparable to the conventional catheter system for quantifying esophageal pH,
but is more comfortable and allows the patient to be more
active during the test period. Of benefit, a pH electrode that
is attached to the esophageal mucosa moves with the mucosa and reduces the risk associated with the catheter pH
probes to “dip down” toward the stomach with each swallow and shortening of the esophagus.
CONCLUSION
Ambulatory 24-hour esophageal pH monitoring allows
the measurement of esophageal acid exposure and when
22
J Clin Gastroenterol, Vol 37, No. 1, 2003
expressed by a calculated composite score is an excellent
technique for identifying gastroesophageal reflux disease.
Since its description in 1974, the 24-hour esophageal pH
composite score has proved to be a durable standard to
identify and quantify gastroesophageal reflux disease by
measuring esophageal acid exposure. The test has a high
sensitivity, specificity and reproducibility. A novel radiotelemetric system has currently been introduced with the
benefit of making the test more acceptable to the patient.
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