Intensive Care Med (1996) 22:220 225

(() Springer-Verlag 1996

M. J. M. Bonten
C. A. Gaillard
R. W. Stockbriigger
F. H. van Tiel
S. van der Geest
E. E. Stobberingh

Received: 14 June 1994

Accepted: 5 April 1995

This study was made possible by a grant

(28-2125) from the Praevention Foundation
M.J.M. Bonten (15N) 9R.W. Stockbriigger
S. van der Geest
Department of Internal Medicine,
University Hospital Maastricht,
P.O. Box 5800 NL-6202 AZ Maastricht,
The Netherlands
C.A. Gaillard
Department of Internal Medicine,
Eemland Hospital, Amersfoort, The
Netherlands
F.H. van Tiel. E.E. Stobberingh
Department of Medical Microbiology,
University Hospital Maastricht,
The Netherlands

ORIGINAL

Assessment of gastric acidity in intensive

care patients: intermittent pH registration
cannot replace continuous pH monitoring

Abstract Objective: To test the accuracy of colour-scaled indicator

papers to measure p H values and to
study the correlation between this
m e t h o d of measuring gastric juice
p H once daily and 24-h continuous
intragastric pH monitoring in intensive care patients.
Desion: The accuracy of indicator
papers was tested in the l a b o r a t o r y
using colourless solutions and aspirated gastric juice and was then
verified with a l a b o r a t o r y p H meter.
Continuous intragastric p H
monitoring was performed in mechanically ventilated ICU patients.
Percentages of time with a p H value
< 3.0 and median p H values by
24-h continuous intragastric p H
monitoring were c o m p a r e d to p H
values measured once daily with
indicator paper.
Setting: A mixed ICU.
Patients." A total of 150 measurements were taken by continuous p H
monitoring in 91 mechanically ventilated ICU patients.
Measurements and results: The correlation between the p H measured
with the indicator paper and subsequently verified with a l a b o r a t o r y
p H meter in colourless solutions
was 0.96 [-regression coefficient
(RC) 0.98, 95% confidence interval
(CI) 0.91-1.05]. Measured in gastric

juice it was 0.95 (RC 0.95, 95% CI

0.88-1.01). The correlation between
median p H values, determined with
24-h continuous intragastric p H
monitoring, and values measured
with indicator papers was 0.39 (RC
0.43, 95% CI 0.26-0.59). The mean
difference in pH, as determined by
the analysis of Bland and Altman
[22], was 0.9 with a SD of 4.7. The
correlation between the percentage
of time with p H < 3.0, as obtained
with continuous registration, and
median gastric p H values (also obtained with continuous registration)
was - 0.94 (RC - 0.06, 95% CI
- 0.06- - 0.05); the correlation between the time and gastric p H
values (measured with indicator paper) was - 0.40 (RC - 0.02, 95%
CI - 0.03 - 0.02).
Conclusion." The colour-scaled indicator paper is an accurate m e t h o d
of measuring p H values, but there is
a p o o r correlation between gastric
p H values measured once daily and
a total measurement derived from
24-h continuous intragastric p H
monitoring. Changes in intragastric
p H values cannot be accurately
studied when measuring acidity
once daily. The influence of various
treatment regimens on intragastric
acidity in relation to the development of gastric colonization and

221

nosocomial pneumonia should be

investigated either with continuous
intragastric monitoring or with
frequent measurements in aspirated
gastric juice.

Key words Pneumonia 9 Gastric

p H . Colonization" Stress ulcer
prophylaxis. Nutrition

Introduction

Patients and methods

Gastric colonization has been assumed to be important in the pathogenesis of nosocomial pneumonia
in mechanically ventilated ICU patients [1,2].
Bacterial overgrowth in the stomach is facilitated by
alkalinization of the intragastric environment [3-5].
Therefore, maintainance of intragastric acidity has
been used to prevent gastric colonization and pneumonia in mechanically ventilated ICU patients [6 13].
In all but one study the effect of stress ulcer prophylactic agents and enteral feeding on intragastric pH was
determined with colour-scaled indicator papers in
aspirated gastric juice samples [6 13]. Measurements were performed intermittently, in some studies
once daily [10,12 14] or with an unknown frequency [6].
It is, however, questionable whether results obtained by randomly measured intragastric pH values
with indicator papers are valid for definite conclusions
regarding modulation of intragastric acidity. In the
first place, physiologic diurnal changes of intragastric
acidity probably are not registered when samples
are obtained infrequently. Secondly, two studies
demonstrated poor accuracy of indicator papers,
when compared to values concomitantly obtained with
pH electrodes [15, 16]. The latter observations
are in contrast to those described by Levine and
coworkers, who found a good correlation between spot
measurements obtained by litmus paper and those obtained by an intragastric antimony pH probe [17].
However, both pitfalls can be overcome by using
computerized continuous intragastric pH measurement with intraluminal electrodes. In other research
settings this method has become an established technique because of its high accuracy and reproducibility
[18 21].
We determined the accuracy of colour-scaled
indicator papers for the determination of pH in
gastric samples of intensive care patients and compared
the results of this method with a summary pH
measure obtained by continuous intragastric pH
monitoring.

Accuracy of indicator paper

The accuracy of colour-scaled indicator papers was studied in two in
vitro experiments. In the first experiment 60 measurements with
indicator paper (Schleicher & Schiill, range: 1.0 12.0 with 23 steps of
0.5) were performed using a blind test in colourless solutions with
pH values ranging from pH 1.0 to 7.5. As a standard, the pH values
of these solutions were verified with a laboratory pH meter (PHM82
Standard pH Meter, Radiometer a/s Copenhagen, Denmark). To
account for factors that possibly affect the accuracy of measurements with pH paper in gastric samples, in a second experiment the
pH values of 93 random and unprocessed gastric samples were
determined in parallel with a laboratory pH meter and with indicator paper. In all cases measurements with pH paper were taken
first and all laboratory measurements were performed by the same
technician.

Patients
For the in vivo comparison of random and continuous pH monitoring, 91 pa/ients admitted to the ICU who needed mechanical ventilalion were prospectively enrolled in the study. All patients were
endotrachcally intubatcd, had a nasogaslric tube, and received
either sucralfatc or antacids l\)r stress ulcer prophylaxis.
The protocol was approved by lhe institutional review board of
the hospital, and inl\)rmed consent was obtained fi-om all participants, or if this was not possible because of the clinical condition,
consent was obtained from a representative of the family.

lntragastric pH recording
A plI stomach probe with a glass electrode tip (LoT 440. lngold
AG, U r d o f f Switzerland) was transnasally positioned m the stomach with the tip situated approximately 10cm below the cardia.
The position of Ihe tip was verilied by radiography. The dislance
from tip to nostrils was kept constant lk)r the entire recording
period. Recording of intragastric acidity was per%rlned for 24 h and
pit values were registered every 4 s. The plt data were stored in
a I)igitrapper Mk Ill (Syneclics Medical, Alphen aan den Rijm The
Netherlands) and after the procedure transferred to a personal
computer. Analysis was perl\mncd using Esophogram software
(Gastrosoft Inc., Synectics Medical). The median value and the
percentage of time with a pH <3.0 during the recording period were
calculated from all measurements. Electrodes and recorders were
calibrated at 20 C using commercial buffer solutions at pH 7.0 and
1.3 (lngold AG), before starting every cxperiment and rcpcated
af|erwards.

222

pH recording of gastric samples

Gastric juice samples of the patients were obtained routinely once
daily at 8.00 a.m. by aspirating gastric fluid into a syringe. Thereafter, pH values were determined with indicator paper. All measurements of pH values with indicator papers were performed by the
same technician, who was unaware of the results of the continuous
intragastric pH measurements.

Data analysis
Because of the non-parametric data, the median pH and the percentage of recording time with a pH value < 3.0 were calculated from
each continuous intragastric pH measurement. The pH value of 3.0
was arbitrarily chosen. The mean pH values from continuous pH
monitoring and the pH values obtained by colour-scaled pH papers
were analysed by the Bland and Altman method [221 and by
calculating the correlation coefficient (r value) and the 95% confidence interval of the regression line.

Results

Accuracy of indicator papers

In the two laboratory experiments good correlations
were observed between pH values measured with indicator papers and those determined with a laboratory
pH meter. The correlation coefficient between the indicator paper method and the pH values of colourless
solutions was 0.96 (RC = 0.98, 95% CI 0.91-1.05). The
correlation coefficient of pH values of gastric samples,
measured in the laboratory with indicator papers and
verified with a laboratory pH meter, was 0.95
(RC -- 0.95, 95% CI 0.88 1.01).

from 24-h intragastric monitoring are listed in Table 1.

The mean pH value of aspirated gastric samples obtained with indicator paper is also listed in Table 1. The
average pH value determined from median values of
continuous intragastric measurements was lower than
the mean pH value, as determined once daily with
indicator paper (4.4 _+ 2.2 SD vs 5.3 + 2.0).
Median gastric pH values and percentages of time
with gastric pH values below 3.0, both obtained with
continuous intragastric pH measurement, are plotted

Table 1 Results of continuous intragastric pH measurements and

the indicator paper technique

Intragastric
pH monitoring
No. of recordings
150"
(91 patients)
Mean of pH values _+ SD
4.4 _+ 2.2 b
Range
0.5 8.0
Mean % of time with pH < 3.0 + SD 34.2 _+ 34.9
Range
0-100
No. of recordings with pH < 3.0
46 (31%)c

100

The average of the median pH values and the average

percentage of time with pH values below 3.0 obtained

5.3 2.0
1.0-8.5

24 (]6%)

-~
eeOo

9
e O

80

4,

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V
O.
a~

60

",'t 9
9

40

7 ~

W O

*o

20

0
I
0

Comparison of once-daily measurements and

continuous intragastric pH monitoring

150

Number of Iong-term measurements performed

b Mean of median values
~Median pH value < 3.0

Patients

In total, 150 episodes of intragastric pH monitoring

were performed in 91 patients. The mean age (_+ SD) of
the patients was 61 _+ 18 years with a range from 19 to
88 years and a mean APACHE II score on admission of
21 (SD = 8) with a range from 6 to 40. Thirty-seven
patients were surgical, 22 medical, 15 pulmonary,
9 trauma and 8 neurological. All patients were mechanically ventilated. In 46 patients more than one episode
of 24-h intragastric pH monitoring was recorded (2
episodes n = 36, 3 episodes n = 7 and 4 episodes n = 3).

Indicator
paper

P
2

4
Median

I
6

I
8

I
10

ci p H

Fig. 1 Correlation between median pH values (median ci pH, xaxis) and the percentage of time with pH values <3.0 (% pH <3,
y-axis), both obtained by continuous intragastric pH monitoring,
r = - 0.9425

223

100

10

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in Fig. 1 (r =
0.94, R C 0.06, 95% CI 0.060.05). In contrast, the correlation between the gastric
pH values, obtained once daily with indicator paper,
and the percentages of time with pH values below 3.0
was only - 0 . 4 0 , ( R C - - 0 . 0 2 ,
95% C l - 0 . 0 3 0.02, Fig. 2).
The median pH values from continuous intragastric
recordings and the corresponding pH value of the indicator paper method are plotted in Fig. 3. Considerable
differences between the two methods were observed.
The analysis according to Bland and Altman [22] is
shown in Fig. 4: The averages ofpH data obtained with
the two methods are plotted against their differences.
The average difference between the two methods was
0.9, S D

OO0

Median ci pH

pH

Fig. 2 Correlation between p H values obtained by indicator papers

(stick pH, x-axis) a n d the percentage of time with pH values < 3 . 0
obtained by c o n t i n u o u s intragastric p H m o n i t o r i n g (% p H < 3 ,
y-axis), r
0.3998

09

410

0~

Ore'

Stick

@@

9 8 oe 9 9
9

aid

W,@O
9

,.

qlNP@ 9

m'

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9

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20

GI,

qn,@

Q,

o f 4.7.

Fig. 3 C o r r e l a t i o n between m e d i a n p H values as o b t a i n e d with 24-h

intragastric m o n i t o r i n g (median ci pH, x-axis) a n d p H wdues as
obtained with indicator papers (stick pH, y-axis), r = 0.3920

"~"

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. . . . . . . .

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'f-~iP-

- - -* . . . . . . . . . . . . . .

I
4

I
6

I
8

5.6

I
10

Mean (ci pH and stick pH)

Discussion

The main feature of the present study is that there is

a poor correlation between the results of gastric pH
values obtained once daily with colour-scaled indicator
paper and summary pH measures obtained with continuous 24-h intragastric pH monitoring. It seems unlikely that the difference between the two methods was
caused by inaccuracies in either one. Continuous
intragastric pH measurements have been validated

Fig. 4 D i s a g r e e m e n t between pH paper (stick pH) and c o n t i n u o u s

pH m o n i t o r i n g (ci pH) values as assessed by the difference between
m e t h o d s ( c o n t i n u o u s m o n i t o r i n g m i n u s pH paper). T h e + 2 SD of
thc diffcrences range is 9.4 pH units

repeatedly [16], and in this study calibration of the

electrodes was performed before each measurement
and verified afterwards. Moreover, the indicator
paper method showed a good correlation with
measurements performed with a laboratory pH meter,

224

both in colourless solutions and in gastric juice. This is in

line with observations made by others [17, 23], although
two other studies have demonstrated a poor accuracy
of the indicator paper method [15, 16]. In one study the
indicator paper method had a sensitivity of 67% and
a specificity of 95% for determining pH values > 4,
taking electrode measurements as the gold standard.
The authors suggested that the inhomogeneous mixture of gastric acid, mucus, bile pigments and antacids
interfered with the accurate measurement of pH values
with the indicator paper [16]. Caballero et al. also
demonstrated poor accuracy of the indicator paper
method, as compared to a standard laboratory meter in
a clinical setting [15]. However, in that study results
were obtained from different hospitals [15]. The fact
that all pH measurements with indicator papers in the
present study were performed by the same technician
might explain the accuracy observed in this study.
It appears that measurements of pH values in aspirated gastric samples performed once daily do not
accurately reflect 24-h pH values in the intragastric
milieu. Our results are in line with the observations
made by others, indicating a good correlation when pH
measurements are performed half-hourly or even hourly [19 21,24]. The need for frequent assessment of
intragastric acidity was also stressed by investigators
who studied the efficacy of antacids to prevent gastrointestinal bleeding in critically ill patients [25, 26].
In these studies it was emphasized that intragastric
acidity should be checked at least every 2 h.
Several studies in which incidental pH measurements of gastric juice were used have addressed the
effect of modifying gastric juice pH on gastric bacterial
colonization and the development of nosocomial pneumonia (Table 2). As demonstrated in Table 2, significant differences in pH values for the different stress
Table 2 F r e q u e n c i e s a n d results
of p H m e a s u r e m e n t s in
aspirated gastric juice u s i n g
colour-scaled indicator paper

Author

D r i k s et al. [6]
T r y b a [7]
K a p p s t e i n et al. [8]
E d d l e s t o n et al. [9]
S i m m s et al. [11]
P r o d ' h o r n et al. [12] e

ulcer prophylactic agents were observed in all studies

[6-9, 11, 12]. However, the frequency of measurements
ranged from 1 to 12 times per day. In the study of Driks
et al. 805 gastric samples were obtained from 130
patients with a mean ICU stay of 10 days, which
implies that gastric acidity was measured every second
day [6]. In addition to the studies listed in Table 2, the
effects of modulation of intragastric aciditiy by gastric
feeding were addressed in three other studies [10, 13, 14].
Heyland et al. compared the influence of acidified gastric feeding (pH 3.5) as compared to nonacidified feeding (pH 6.5) administered either in the stomach or the
duodenum, while Lee et al. and Spilker et al. compared
the effects of continuously or intermittently administered gastric feeding on intragastric acidity [10, 13]. In
these three studies gastric pH was measured once daily
with colour-scaled papers in aspirated gastric juice.
Despite the fact that the mean difference between
once daily and continuous measurements was less than
one pH unit, we feel that the results regarding intragastric acidity from studies where pH values were not
measured continuously should be interpreted with caution. Whether this is a clinically important difference
resulting in different rates of colonization and pneumonia remains to be established.
Computerized continuous intragastric monitoring
is expensive and may not be available to all investigators. Moreover, computerized intragastric pH monitoring may not be feasible in patients who remain in
a study protocol for weeks to months. Therefore, the
minimal number of measurements in a 24-h period that
is required to determine accurately long-term intragastric acidity with indicator paper in aspirated gastric
juice should be established by comparing this method
with different frequencies of measurement and computerized intragastric monitoring.

Frequency
of m e a s u r e m e n t
(per day)

P r o p o r t i o n of samples
with P H < 4.0 (%)
Test C o n t r o l s

Unknown
3
_< 6
4
12

47.9 a 25.3 b (p < 0.001)

46.5 a t0.4 c (p < 0.01)

1.3-1.5

20.0 a 11.1 c
9.4 a (p > 0.05)
46.7 a 3.9 c
10.9 d

Test patients received sucralfate

b C o n t r o l patients received antacids a n d / o r H 2 a n t a g o n i s t s
c C o n t r o l patients received antacids
a C o n t r o l patients received H2 a n t a g o n i s t
e Values are expressed in m e d i a n p H per patient

Mean pH
Test C o n t r o l s

4.34 ~'
4.26 a
4.73 a
4.30 a

4.84 d
5.50 d
5.55 ~
5.06 d
7.10 c
6.27 d

(P
(P
(P
(P

<
<
<
>

0.05)
0.01)
0.01)
0.05)

(P < 0.0001)

225

Despite the excellent accuracy of indicator papers,

as determined in the present study and by others
[17], we conclude that changes in intragastri
pH values cannot be accurately studied when measuring acidity only once daily or even less frequently.
The correlation between modulation of intragastric

acidity by different treatment regimens and the subsequent development of gastric bacterial colonization
and nosocomial pneumonia should be re-evaluated using either continuous intragastric pH monitoring or
a frequent measurement of pH in samples of aspirated
gastric juice.

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