(Chest. 1999;115:102-108.)
© 1999
American College of Chest Physicians
Effects of Sodium Bicarbonate Administration on the Exercise Tolerance of Normal Subjects Breathing Through Dead Space*
Richard W. Light, MD, FCCP;
Ming-Jen Peng, MD;
David W. Stansbury;
Catherine S. H. Sassoon, MD, FCCP;
Judith A. Despars, RN and
C. Kees Mahutte, MD, PhD, FCCP
*
From the Department of Medicine of the Veterans Administration Medical
Center, Long Beach Pulmonary Disease Service, Saint Thomas Hospital and
Vanderbilt University, Nashville, TN.
 |
Abstract
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Study objective: The purpose of this study was to
determine whether the administration of sodium bicarbonate to normal
individuals would increase their PaCO2 and
thereby decrease the ventilatory requirements at a given workload.
Design: In this double-blind crossover study, six normal
men ingested either 3 mEq/kg NaHCO3 or 1 mEq/kg NaCl once a
day for 5 days, in addition to 40 mg of furosemide and 40 mEq KCl.
After each 5-day treatment, the subjects underwent a symptom-limited
maximal bicycle ergometer exercise test while breathing through
external dead space (with a volume of approximately 50% of their
FEV1), a second exercise test without any external dead
space, and an assessment of their respiratory response to
hypercapnia.
Results: The administration of the
NaHCO3 resulted in a significant increase in the arterial
HCO3- from 20.8 to 24.0 mEq/L and a
significant increase in the PaCO2 from 31.7 to
36.9 mm Hg at rest that persisted during exercise. During exercise
periods with the added dead space, the Borg scores were significantly
lower at each workload after the subjects received bicarbonate,
but the maximal exercise level did not increase. The mean (± SD)
slope of the mouth occlusion pressure response to hypercapnia was
significantly lower after the administration of NaHCO3 than
after NaCl, respectively: 0.73 ± 0.41 vs 1.27 ± 0.97 cm
H2O/mm Hg.
Conclusion: From this study we
conclude that the administration of NaHCO3 results in a
significant increase in the PaCO2, decreases
the ventilation and the Borg score at equivalent workloads, and
decreases the hypercapnic response in normal
individuals.
Key Words: dead space • exercise • metabolic alkalosis
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Introduction
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The
exercise capacity of many patients with chronic lung disease is limited
by their ventilatory capability.1
In order to increase the
exercise capacity of these individuals, their ventilatory capabilities
must be increased or their ventilatory requirements decreased.
When metabolic alkalosis is induced in a normal subject, the body's
response is an attempt to maintain a nearly normal pH by increasing the
PaCO2 via a decrease in the alveolar
ventilation.2
The increase in the
PaCO2 should decrease the required
alveolar ventilation at a given level of exercise because the constant
rate of carbon dioxide (CO2) elimination,
expressed here as carbon dioxide output
(
CO2), is proportional to the
product of the PaCO2 and the alveolar
ventilation. As alveolar ventilation decreases, the required
minute ventilation (E) at each exercise level is
decreased.
The exercise capability of normal subjects is limited by their cardiac
function.3
,4
Consequently, at exhaustion normal
individuals do not use all of their ventilatory capacity.5
However, if normal individuals exercise while breathing through added
external dead space, they may have no ventilatory reserve at
exhaustion5
and, accordingly, may be ventilation limited.
The objective of this study was to determine whether the exercise
capacity of normal individuals who are made ventilation limited by
breathing through added external dead space would be increased with the
ingestion of sodium bicarbonate. We hypothesized that the increase in
the serum bicarbonate level after the ingestion of sodium bicarbonate
would lead to an increase in the
PaCO2, and thereby would decrease
their ventilatory requirements at a given workload.
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Materials and Methods
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Study Population
Six normal, nonsmoking, male volunteers participated in the
study (Table 1
). None had a history of cardiac or pulmonary disease, and all had
normal spirometry. All of the subjects signed written consent forms
approved by the institutional review board at the Long Beach Veterans
Administration Medical Center.
Preliminary Studies
Prior to the main study, the subjects were familiarized with
exercise testing on the bicycle ergometer. They also performed a
maximal exercise test with an added external dead space having a
displacement volume approximately equal to 50% of their
FEV1. In order to ensure that the subjects were
ventilation limited while exercising with the dead space, we required
that all of the following conditions were met: (1) the maximum workload
tolerated with the dead space had to be less than that tolerated
without the dead space; (2) the subject had to state that the primary
reason for ceasing to exercise with the added dead space was shortness
of breath; and (3) at the end of the exercise with dead space, the
end-tidal PCO2 had to be at least as
high as when the subject was at rest.
Study Medications
The main study was a randomized, double-blind crossover study
comparing the effects of 3 mEq/kg NaHCO3 or 1
mEq/kg NaCl treatment administered for 5 days on the exercise capacity
of normal individuals who were exercising while breathing with and
without added dead space. The subjects were also given 40 mg of
furosemide and 30 mEq KCl for the 5-day period. There were two
different treatment periods separated by at least a 7-day washout
period. The doses of NaHCO3 and NaCl were
packaged in identically appearing capsules, and equal portions of the
NaHCO3 or NaCl were given three times a day.
Study Sequence
Once the subjects had taken their assigned medications for the
5-day period, they reported to the pulmonary exercise laboratory after
not eating breakfast. After an arterial line was inserted in each of
the subjects, they underwent a symptom-limited maximal exercise test
with dead space. After a 30-min rest, they underwent a symptom-limited
maximal exercise test without dead space. After another 30-min rest,
their respiratory responses to hypercapnia were tested.
Dead Space
The dead space was added by inserting lengths of large-bore
flexible tubing (3.8-cm internal diameter) between the mouthpiece and
the two-way valve (Model 2700; Hans-Rudolph; Kansas City, MO),
as previously described.6
The total resistances were
essentially equal to the resistance of the breathing valve and were not
altered measurably by the addition of dead space. Given that our
preliminary studies have shown that some individuals develop marked
hypoxia during exercise with dead space, the present studies were
conducted with the subject breathing sufficient supplemental
O2 to maintain arterial oxygen saturation at
> 90%. No attempt was made to ensure that the subjects received the
same amount of supplemental O2 at each workload
on the two different tests.
Maximal Exercise Test
The testing was performed in an incremental (30 W/min) fashion
leading to a symptom-limited maximum on an electrically braked cycle
ergometer (BV Cycle Ergometer, type 18870; Gould Godart; Bilthoven, The
Netherlands) in a manner similar to that previously
described7
,8
in our laboratory. The arterial oxygen
saturation was monitored and recorded with an oximeter (Biox 3700;
Ohmeda Corp; Louisville, CO). The heart rate was monitored with
a Diascope DS S21 (Simonson and Weel; Denmark). Expired gas was
collected over 30-s intervals. All metabolic measurements were made by
metabolic measurement cart (Horizon 4400; Sensormedics; Yorba
Linda, CA). The rate of O2 consumption
(O2) and the
CO2 were calculated from
measurements of E and from the composition of
inspired and expired gas and expressed at standard temperature (and)
pressure, dry. During the last 30 s at each power output,
measurements of cardiac and respiratory frequencies and a modified Borg
scale score9
were obtained. In calculating the Borg score,
the patient was requested to rate the magnitude or severity of
breathlessness. The values obtained from the last completed one-half
min of cycling were considered to be the maximal values.
Arterial blood sampled from the arterial line was drawn into
heparinized syringes, placed in an ice-water bath, and analyzed within
20 to 60 min with standard blood gas electrodes (model 1306;
Instrumentation Laboratories; Lexington, MA). The samples were
obtained at rest, after breathing through the dead space at rest for 5
min, and during the last 15 s at every other exercise level.
Hypercapnic Respiratory Response
The hypercapnic respiratory response was measured using the Read
rebreathing technique.10
The subjects were seated
comfortably at the mouthpiece, with the noseclip in place, breathing
room air until the end-tidal PCO2 was stable.
They then started rebreathing a mixture of approximately 7%
CO2 in O2. Once a
satisfactory rebreathing plateau was obtained, the rebreathing was
continued until the PCO2 had risen at
least 12 mm Hg above the rebreathing
PCO2 plateau, or for 4 min, whichever
came first. The tidal volume (VT) was measured with a dry
rolling seal spirometer (Model 131; P.K. Morgan; Gillingham,
KY). The PCO2 was monitored at the
mouthpiece with a rapid infrared CO2
analyzer (Model LB-3; Beckman Instruments; Fullerton, CA). Mouth
pressure was recorded with a differential pressure transducer
(Model MP 45; Validyne Engineering Corp; Northridge, CA). Approximately
every 15 s, without the subject's knowledge, the inspiratory side
of the rebreathing circuit was occluded for < 0.2 s by a noiseless
and vibration-free pneumatic device (Series 9300, Balloon Valve;
Hans Rudolph). The VT, mouth pressure, and
PCO2 were continuously recorded on a
four-channel model recorder (Model 7754 B; Hewlett-Packard; Andover,
MD). After completion of the test, the ventilatory responses and
mouth occlusion pressure at 0.1 s after onset of inspiratory effort
(P0.01) responses were plotted against the
PCO2, and the slopes for the
responses were obtained by the least-squares linear regression
analysis.
Data Analysis
Statistical analysis was performed using Student's t
test for matched pairs. Differences were considered statistically
significant when p < 0.05. All of the values are expressed as the
mean (± SD).
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Results
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Rest
The administration of sodium bicarbonate resulted in a significant
increase in the arterial HCO3-
both at baseline and when the subjects were breathing through dead
space (p < 0.05), as shown in Table 2
. As expected, the subjects developed a respiratory compensation for the
increased HCO3- such that the
arterial pH was not significantly higher after the bicarbonate
treatment than it was after the saline treatment. The mean
PaCO2 was 5.2 mm Hg (16.5%) higher
after the administration of NaHCO3 than it was
after saline administration at baseline (p < 0.05), as shown in
Table 2
. When the subjects breathed through the dead space, the
PaCO2 increased by a mean of about 8
mm Hg (p < 0.01), irrespective of whether or not they had received
bicarbonate. At rest, the PaO2 was
very similar whether the subjects had received bicarbonate or placebo.
After the subjects had received NaHCO3, their
E at rest was significantly lower than after they
received NaCl (p < 0.05). There was a comparable decrease in the
ventilation (approximately 4 L/min) while the subjects breathed through
dead space at rest (Table 2
), but this difference did not achieve
statistical significance (p > 0.05). The ventilatory equivalents for
both O2
(E/O2) and
CO2 (E/
CO2) tended to be lower after
the administration of NaHCO3, but the differences
did not achieve statistical significance. The
E/O2 was
not obtained with dead space because we could not measure the
O2 accurately while the
subjects were receiving supplemental O2.
The E/CO2
with the dead space is very high because of the dead space.
During Exercise
The changes in the blood gases observed at rest tended to persist
during exercise. During exercise with and without dead space, the mean
HCO3-, pH, and
PaCO2 were significantly higher after
the subjects had taken bicarbonate than after they had taken placebo
(p < 0.001). The mean PaCO2 was
3.6 mm Hg higher when the subjects exercised without dead space
(p < 0.001) as shown in Figure 1 , top
, and was 6.2 mm Hg higher while the subjects exercised with dead space
when the data from all workloads was combined (p < 0.001), as shown
in Figure 1
, bottom. The degree to which the
PaCO2 was elevated after the subjects
received bicarbonate was approximately the same at all levels of
exercise (Fig 1
, top and bottom). The
PaO2 was similar after bicarbonate
and after placebo.
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Figure 1. Figure 1, Top: The mean
PaCO2 at rest and at the various workloads
while the subjects breathed without added dead space.
Bottom: The mean PaCO2 at rest
and at the various workloads while the subjects breathed through added
dead space
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The ingestion of bicarbonate for 5 days did not increase the maximum
workload for the subjects while they were breathing with or without
dead space (Table 3
). Along the same lines, the
O2max and the
CO2max were virtually
identical irrespective of whether the subjects ingested placebo or
bicarbonate (Table 3
). The mean maximal workloads attained while
exercising with dead space were significantly reduced compared to the
workloads attained without dead space irrespective of whether the
subjects had ingested placebo or bicarbonate (p < 0.05).
We next examined our data on the highest equivalent workload attained
by both treatment groups (Table 4
). During exercise with or without dead space, the mean
HCO3- was significantly lower
after placebo ingestion than after bicarbonate ingestion. There were no
significant differences in the PaCO2,
O2,
CO2, E,
E/O2, and
E/CO2 when
the subjects exercised after ingesting placebo or bicarbonate (Table 4
).
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Table 4. Summary of Mean Results for all Subjects at the
Highest Equivalent Workload Attained, While Exercising With and Without
Dead Space*
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When the data were examined at each workload, there were no significant
differences in the E in the two treatment groups at
any of the workloads while exercising with or without dead space (Fig 2
)
.
When the subjects exercised without dead space, the mean Borg
score was nearly identical regardless of the treatment group. All the
Borg scores were low when the subjects were exercising without dead
space. In contrast, when the subjects exercised with dead space (Fig 3
), the mean Borg score was lower at all exercise levels after the
subjects had received bicarbonate. When all of the Borg scores while
exercising with dead space were compared, the scores of the bicarbonate
group were significantly lower than the placebo group (p < 0.001).
Hypercapnic Responses
The mean slope of the P0.01 response to
hypercapnia was significantly lower after NaHCO3
than after NaCl, respectively: 0.73 ± 0.41 vs 1.27 ± 0.97 cm
H2O/mm Hg (p < 0.05), as shown in Table 2
. The
mean slope of the ventilatory response to hypercapnia was also lower
after bicarbonate than after saline, respectively: 3.56 ± 2.23 vs
4.27 ± 3.22 L/min/mm Hg, but the differences were not statistically
significant (Table 2
).
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Discussion
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In the present study, we have demonstrated that the administration
of 3 mEq NaHCO3/kg/d for 5 days to normal
subjects resulted in a significant increase in blood bicarbonate
levels. The subjects compensated for the increased bicarbonate with an
increase in their PaCO2 of about 5 mm
Hg at rest. During exercise with or without the addition of dead space,
the PaCO2 after bicarbonate ingestion
was 4 to 6 mm Hg more than the PaCO2
without bicarbonate at all levels of exercise. Although the maximal
workload was not increased after the ingestion of bicarbonate, there
was a significant reduction in the Borg score after the subjects
received bicarbonate while exercising with added dead space. The
P0.01 response to hypercapnia was significantly
reduced after the ingestion of bicarbonate.
In the present study we were successful in inducing an increase in the
mean serum bicarbonate levels. The increase of 3.2 mEq/L was almost
completely compensated for by the respiratory system because the
PaCO2 increased by 5.2 mm Hg while
the pH increased by only 0.01 units (Table 2
). The increase in the
PaCO2 is about what one would expect
from this increase in the HCO3, because for each
mEq increase in the HCO3 an increase of 0.7 to
1.5 mm Hg in the PaCO2 can be
expected.11
,12
Other investigators have reported similar
results. Javaheri and Kazemi12
administered 150 to 400 mg
of NaHCO3 for 7 days and reported that the mean
PaCO2 increased by 6 mm Hg. Forster
and Klausen13
gave 700 mg NaHCO3 for
8 to 10 days and reported that the HCO3 increased
3.2 mEq/L, while the PaCO2 increased
from 41.4 to 44.2 mm Hg.
The administration of the sodium bicarbonate resulted in a decrease in
the E at rest. In the present study, the
E was 8.33 L/min after the subjects received the
bicarbonate, compared to 11.33 L/min after they received placebo.
Javaheri and Kazemi12
reported a similar reduction in
ventilation. Given that the induction of a metabolic alkalosis results
in an increased PaCO2, one would
expect that the E would decrease, because in the
steady state: E =
(CO2 x
760)/[PaCO2 x (1 -
VD/VT)] (1) If the
CO2 and the physiologic dead
space ventilation (VD/VT) stay the same, the
E should decrease if the
PaCO2 increases.
There have been many previous studies on the effects of sodium
bicarbonate administration on the exercise performance of normal
individuals. It has been hypothesized that increased levels of
bicarbonate will at least partially compensate for the increased lactic
acid levels in the blood during exercise above the anaerobic threshold
and will, therefore, increase the exercise tolerance. Several studies
have demonstrated an improved performance after the administration of
bicarbonate;2
,14
,15
,16
,17
however, a comparable number have
demonstrated no improvement.18
,19
,20
These conflicting
results indicate that the net effect of bicarbonate administration on
the exercise tolerance of normal individuals is, at most, small.
Previous reports have come to opposite conclusions regarding the effect
of the administration of bicarbonate on the ventilatory response to
exercise. Jones et al2
reported that 3 h following
the ingestion of 0.3 g/kg NaHCO3, the
E (± SD) at 33% of the maximal output decreased
from 32.4 ± 6.2 to 28.1 ± 7.1 L/min, and the E
at 66% of the maximal output decreased from 70.6 ± 17.6 to
67.2 ± 14.7 L/min. In contrast, other
researchers13
,20
,21
have not been able to document a
significant decrease in the E in normal individuals
during exercise after bicarbonate administration. In the present study,
we were unable to document a significant decrease in the
E during exercise after bicarbonate administration.
When our subjects exercised with the added dead space, they appeared to
be ventilation limited. They stopped exercising because of shortness of
breath, and the mean PaCO2 at maximal
exercise was above 50 mm Hg (Fig 1
, bottom). However, after
bicarbonate administration and exercising with dead space, the subjects
were not able to achieve a higher workload, and the
E did not change significantly. Surprisingly (see
Equation 1), the E at a given workload did not
decrease; whereas, the PaCO2 had
increased by more than 5 mm Hg, and the
CO2 remained the same.
In the present study, the administration of bicarbonate resulted in a
significant reduction in the P0.01 response to
hypercapnia. To our knowledge, this relationship has not been examined
previously. However, Javaheri and Kazemi12
did report that
the ventilatory response to hypercapnia was reduced after the induction
of metabolic alkalosis, but they did not assess the
P0.01 response. After bicarbonate administration,
the mean slope of our ventilatory responses was reduced but the
differences did not reach statistical significance. It is certainly
possible that the lower Borg scores of the bicarbonate group exercising
with dead space are related to the reduction in the
P0.01 response to hypercapnia.
From this study, we conclude that in normal individuals
NaHCO3 administration results in a significant
increase in the PaCO2 and a
significant decrease in the hypercapnic P0.01
response. When the bicarbonate subjects exercised with added dead
space, the PaCO2 tended to be
significantly higher at all levels of exercise. Importantly, the degree
of dyspnea at all workloads as measured by the Borg score is
significantly lower after ingesting bicarbonate than after ingesting
saline. These results suggest that the exercise capacity of
ventilation-limited subjects could possibly be improved with the
administration of sodium bicarbonate.
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Acknowledgements
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ACKNOWLEDGMENT: The authors thank Dr. Dong-sheng Cheng for his
assistance in creating the illustrations and for his critical review of
the manuscript, and Ms. Sheila Rupp for her secretarial assistance and
her review of the manuscript.
|
Footnotes
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Correspondence to: Richard W. Light, MD, Director Pulmonary
Diseases, Saint Thomas Hospital, 4220 Harding Road, Nashville, TN
37202
Abbreviations:CO2 = carbon dioxide; O2 = oxygen;
P0.01 = mouth occlusion pressure at 0.1 s after onset of
inspiratory effort; CO2 = carbon
dioxide output; VD/VT = physiological dead
space ventilation; E = minute ventilation;
E/
CO2 = ventilatory equivalent for
CO2; E/
O2 = ventilatory equivalent for
O2; O2 = oxygen
consumption; VT = tidal volume
Received for publication January 23, 1998.
Accepted for publication August 11, 1998.
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Abstract
Introduction
