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Department of Anesthesiology, Center for Hyperbaric Medicine and Environmental Physiology, Duke University Medical Center, Durham, North Carolina 27710
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Physiological dead space (VDS), end-tidal CO2 (PETCO2), and arterial CO2 (PaCO2) were measured at 1 and 2.8 ATA in a dry hyperbaric chamber in 10 older (58-74 yr) and 10 younger (19-39 yr) air-breathing subjects during rest and two levels of upright exercise on a cycle ergometer. At pressure, VD (liters BTPS) increased from 0.34 ± 0.09 (mean ± SD of all subjects for normally distributed data, median ± interquartile range otherwise) to 0.40 ± 0.09 (P = 0.0060) at rest, 0.35 ± 0.13 to 0.45 ± 0.11 (P = 0.0003) during light exercise, and 0.38 ± 0.17 to 0.45 ± 0.13 (P = 0.0497) during heavier exercise. During these conditions, PaCO2 (Torr) increased from 33.8 ± 4.2 to 35.7 ± 4.4 (P = 0.0059), 35.3 ± 3.2 to 39.4 ± 3.1 (P < 0.0001), and 29.6 ± 5.6 to 37.4 ± 6.5 (P < 0.0001), respectively. During exercise, PETCO2 overestimated PaCO2, although the absolute difference was less at pressure. Capnography poorly estimated PaCO2 during exercise at 1 and 2.8 ATA because of wide variability. Older subjects had higher VD at 1 ATA but similar changes in VD, PaCO2, and PETCO2 at pressure. These results are consistent with an effect of increased gas density.
pulmonary gas exchange; hypercapnia; hyperbaric; end-tidal CO2; arterial CO2; aging
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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HYPERCAPNIA IS A WELL-DESCRIBED consequence of hyperbaric exposure, the mechanisms of which are incompletely understood (31, 48). Many studies in the past half century have described elevated end-tidal PCO2 (PETCO2) in exercising subjects, often higher than 60 Torr, at pressures of 3.0 atmospheres absolute (ATA) and greater (14, 19, 24, 37, 40, 54). Measurements of arterial CO2 tension (PaCO2), although less common, confirm that hypercapnia of varying degrees occurs during exercise at high atmospheric pressure (28, 47) and with dense gas breathing at 1 ATA (57). Hypercapnia is a potentially serious problem for divers, contributing to central nervous system O2 toxicity, inert gas narcosis, and loss of consciousness (31).
The cause of hypercapnia in divers is multifactorial. Mechanisms that
may contribute include the following. 1) Hypoventilation secondary to increased work of breathing may be due to the effects of
increased gas density (10). Expiratory flow is limited by an increase in airway resistance, and inspiratory elastic work is
increased because of breathing at a higher lung volume
(51). In immersed divers, the work of breathing is further
increased by a redistribution of blood into the thorax, causing a
decrease in lung compliance (1). 2) A blunted
ventilatory response to exercise with inappropriately low minute
ventilation (
E) (28, 31) may be due to
factors other than gas density. Possible causes of this phenomenon
include self-selection among divers, an acquired adaptation to
hyperbaric exposure, or an alteration in central regulatory mechanisms
(15, 27). 3) Increased physiological dead space
(VDS) (46, 47) may be possibly due to changes
in the distribution of ventilation as a consequence of dense gas breathing. Increased anatomic VDS as a result of an
enlarged functional residual capacity may contribute (51).
Although increased VDS does not by itself lead to
hypercapnia, it will do so if it is not accompanied by a compensatory
increase in total ventilation.
Of these factors, the increase in physiological VDS is the least explored. Saltzman et al. (46) reported elevated Bohr VDS in resting subjects breathing dense gas mixtures at increased atmospheric pressure (up to 7.7 g/l at 7 ATA). The first evidence that changes in VDS may contribute to hypercapnia during hyperbaric exercise was reported by Salzano et al. (47), who found significant hypercapnia and very large increases in VDS and VDS-to-tidal volume (VT) ratio (VDS/VT) in divers performing exercise in a dry chamber at the extreme simulated depths of 460 and 650 m (pressures 47 and 66 ATA and gas densities 12.3 and 17.1 g/l, respectively). Increased VDS/VT and PaCO2 have also been observed in resting subjects breathing dense gas mixtures at 1 ATA (57). Measurements of VDS at shallower depths have not been reported.
If VDS were to increase at commonly encountered recreational depths, older divers especially might be at increased risk of respiratory impairment. Aging is associated with increased VDS (5, 11, 38, 43), loss of respiratory muscle strength (21, 26), and decreased lung elastic recoil and chest wall compliance (21). Older subjects also exhibit decreased ventilatory responses to exercise and hypercapnia (8, 42). An increase in VDS could accentuate relatively minor changes in resting gas exchange in older divers and increase the risk of CO2 retention.
Furthermore, although PETCO2 closely estimates PaCO2 in young, healthy individuals at rest (41, 44), its accuracy has not been assessed under hyperbaric conditions. As an estimate of PaCO2, capnography is falsely high during conditions associated with increased CO2 production, such as exercise (44, 55), and falsely low in the presence of increased heterogeneity of ventilation or increased VDS (34, 35), which may occur during diving or with normal aging (5, 12). Therefore, under hyperbaric conditions, PETCO2 may be less accurate in all age groups as an estimate of PaCO2.
The primary goal of this study was to examine VDS at a relatively shallow depth of 18.3 m of sea water [60 ft of sea water (fsw)], equivalent to 2.8 ATA, and determine whether the changes in VDS observed at extreme pressures also occur at a simulated depth commonly encountered by recreational divers. Additional goals of this study were to establish the degree of hypercapnia experienced by both younger and older divers during moderate exercise at 2.8 ATA and to compare capnography and direct arterial measurement of CO2 to evaluate the accuracy of PETCO2 as an estimate of PaCO2 across a range of ages.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects. After institutional approval and informed consent, 20 subjects were studied. Subjects were divided into two groups by age [younger (Y), 19-39 yr; older (O), 58-74 yr] and screened for cardiac and pulmonary disease by medical history, physical exam, posterior-anterior and lateral chest radiographs, spirometry [forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)], and treadmill electrocardiogram (ECG) (group O only). Subjects were excluded who had FEV1/FVC < 0.70, contraindications to diving, clinical evidence of heart or lung disease, or pregnancy.
Apparatus. The study took place in a dry hyperbaric chamber (volume 40.5 m3). The temperature was adjusted for comfort between 22 and 24°C (surface) and 24 and 27°C (pressure). One physician and two attendants were present in the chamber and in communication with an outside attendant at all times. Standard hyperbaric safety procedures were observed.
Subjects sat on a mechanically braked bicycle ergometer (model 818, Monark Exercise, Vansbro, Sweden), which was fitted with electrical work rate and rpm outputs. After abrasive skin preparation, a three-lead ECG was applied and used to determine heart rate. At the beginning of the study day, subjects were instrumented in the radial artery with a 20-gauge arterial catheter with the use of sterile technique and local anesthesia (1% lidocaine). The catheter allowed periodic blood samples to be drawn and was connected to a transducer (model 42370-01, Abbott Critical Care, Morgan Hill, CA) placed 5 cm inferior to the sternal angle, from which systolic, diastolic, and mean pressures were monitored. To prevent a fall in the event of syncope, subjects wore a safety harness that was attached via a pulley system to the roof of the chamber. Subjects breathed dry air from a 150-liter bag connected to a low-resistance mouthpiece with one-way valves to allow separation of expired and inspired gases (model 2700, Hans Rudolph, Kansas City, MO). The inspired loop included a Fleisch no. 4 pneumotachometer, which was used to record breathing frequency. Expired gas was collected in leak-tested 100-liter Douglas bags (WE Collins, Braintree, MA), which were opened and closed with a three-way stopcock (model 2100, Hans Rudolph). Components of the breathing loop were connected by leak-free tubing (1
Experimental protocol. The experimental protocol consisted of trials performed first at the surface and then repeated after a 20- to 30-min break at a pressure of 2.8 ATA (corresponding to a simulated depth of 60 fsw or 18.3 m of sea water). We did not randomize the order of surface and pressure experimental protocols because of the potential for initiating decompression illness by performing heavy exercise immediately after decompression. After spirometry, subjects performed the following conditions while sitting upright on the bicycle: 1) rest (5 min); 2) exercise 1 (6 min); and 3) exercise 2 (6 min). Atmospheric pressure and chamber temperature were recorded for each condition.
Exercise levels were based on each subject's level of physical fitness, such that exercise 1 could easily be maintained for 6 min and exercise 2 would be strenuous but would not exceed the subject's maximal exercise capacity. For the purposes of this experiment, a value of 95% of the subject's predicted maximum heart rate (estimated by 220 minus age in years) was used as a guide to exercise capacity. Determination of each subject's maximal O2 consumption (O2) was not
performed because the qualitative effects of exercise were more
important to the outcome variables than the exact level of exercise
performed. To allow for a possible effect of exercise above the aerobic
capacity on gas exchange variables during exercise 2,
comparisons were also made for all variables during exercise
1. When possible, the same exercise levels were performed at 1 and
2.8 ATA, as determined by subject comfort and fatigue.
Work rates were achieved by adjusting the work load on the ergometer
while the subjects pedaled at 80 rpm. Between each exercise level,
subjects rested until heart rate had returned to baseline or for at
least 10 min. Between trials at 1 and 2.8 ATA, subjects rested for
30-60 min.
At the third minute of rest, expired gases were collected for at least
2 min. At the fifth minute of exercise, two bags of expired gases were
collected sequentially for 1 min each. Values from the fifth and sixth
minutes were compared to verify steady state. Values from the sixth
minute were used in all analyses. At the end of each recording session,
gas samples were taken from the inspired and expired Douglas bags in
100-ml wetted, gas-tight glass syringes. The expired gas volume was
measured by evacuating each bag to a pressure of 
5 cmH2O
through a calibrated gasometer (model DTM 325-4, American Meter,
Nebraska City, NE). Gas analysis was performed on a gas chromatograph
(model 3800, Varian, Walnut Creek, CA) for O2 and
CO2 concentrations.
During the third minute of rest and the sixth minute of each exercise
period, two arterial blood samples were collected anaerobically over
15-30 s in heparinized gas-tight glass syringes. One sample was
analyzed immediately within the chamber for pH, arterial O2 tension (PaO2), and PaCO2
with a blood-gas analyzer calibrated for use at the ambient pressure of
the chamber (model Synthesis 15, Instrumentation Laboratory, Lexington,
MA). The second sample was stored on ice and analyzed within 30 min of
collection for hemoglobin concentration and O2 saturation
with a CO-oximeter (model 482, Instrumentation Laboratory) located
outside the chamber.
The time at simulated depth ranged from 52 to 60 min. Decompression
protocols were derived from a conservative modification of US Navy air
decompression tables (following tables for 70 fsw and the next longest
time). Decompression proceeded at a rate of 30 ft/min from the
simulated depth of 60 to 30 fsw, and then at 10 ft/min to 10 fsw, where
an 8- to 14-min stop occurred to ensure adequate N2
elimination. Decompression then continued at 2 ft/min from 10 fsw to
the surface. All personnel (subjects and experimenters) breathed 100%
O2 during decompression from a pressure equivalent to a
depth of 50 fsw to the surface.
Equipment calibrations. The blood-gas analyzer was calibrated at the beginning of each surface and pressure session by use of standard calibration gases. The capnograph was calibrated before each period of rest and exercise with gases of known CO2 fraction, from which the partial pressure was determined for each ambient pressure. Calibration gases for blood-gas, gas chromatograph, and capnograph analysis were calibrated by gas chromatography against a single reference gas. Arterial and mouthpiece pressure transducers were calibrated before each period of rest and exercise with an aneroid gauge. The gasometer was calibrated before each experiment and the spirometer and pneumotachometer before each session by use of a 3-liter calibration syringe (standard 3-liter, Collins).
Calculations.
VT was determined from measurements of E
and ventilatory frequency (Vf) and corrected to BTPS. Mixed
expired PCO2
(PECO2) was determined from the
expired gas composition and corrected for water vapor pressure at a
body temperature of 37°C. Alveolar ventilation
(A), alveolar O2 tension
(PAO2),
O2, and CO2 elimination (CO2) were determined from standard
equations. VDS/VT was determined from
simultaneous measurements of PaCO2 and
PECO2 by using the Enghoff
modification of the Bohr equation
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(1) |
Statistical analysis. For data that were normally distributed, values are reported as means ± SD. Otherwise, values are median ± interquartile range. To compare surface (1 ATA) and pressure (2.8 ATA) measures, paired Student's t-test or Wilcoxon's signed-rank test was used, respectively, depending on whether the difference was normally distributed or not. Normality was judged by the Shapiro-Wilk test. Marginal differences between groups Y and O were determined by two-sample t-test or two-sample Wilcoxon rank sum test for continuous data, and by Fisher's exact test for binary data. Bland-Altman analysis (4) was used to compare the accuracy of PETCO2 as an estimate of PaCO2. Weighted Cohen's kappa statistic was used to determine agreement between measurements during the fifth and sixth minutes of exercise as confirmation of steady state.
The measurements of a subject's response under the six different conditions (rest and two levels of exercise at 1 and 2.8 ATA) are necessarily correlated. Thus each of these six measures constitutes a cluster. A mixed-model approach was adopted to account for the variation in the measurements that adjusts for interactions between factors such as age, work rate, and atmospheric pressure. StatXact 4.1 (Cytel Software, Cambridge, MA) and SAS V8.2 (SAS Institute, Cary, NC) were used to analyze the data. A significant difference was defined as P < 0.05. Parameters at rest and exercise were treated as separate variables; therefore, P values were not corrected for multiple comparisons.| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Subjects.
Subject characteristics are presented in Table
1. Subjects in group O were
heavier on average by 9.5 kg and had a higher past prevalence of
smoking (50 vs. 10%); there were no current smokers. Spirometry values
(FVC, FEV1, and FEF25-75) are those
recorded at the surface; when corrected for height and age, percentage
of predicted values was similar between groups.
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Work performed.
Work rates varied depending on each subject's level of physical
fitness and were identical at 1 and 2.8 ATA in all but two subjects
(group O), who performed less work at 2.8 ATA during exercise 2 (Table 1). Percent maximum heart rate was similar at 1 and 2.8 ATA for each exercise, with mean values 73 ± 14 (Y) and 77 ± 11% (O) during exercise 1 and 86 ± 13 (Y) and 96 ± 9% (O) during exercise 2. During both
exercises, average work rates were lower in group O, but
O2 was similar between groups.
O2
was higher and CO2 lower than surface
values (Table 2). These
differences were small but most pronounced during exercise 2 (change in O2 of +0.14 l/min, P = 0.0037; change in
CO2 of 0.14 l/min, P < 0.0001). For both measurements, differences between resting values
were not significant. Because O2 and
CO2 varied with work rate and
atmospheric pressure, ventilatory parameters are plotted as a function
of O2 and PaCO2 is
plotted as a function of CO2.
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E,
VT, and Vf were in excellent agreement (kappa > 0.89, P < 0.00001 for all measurements). Measurements of
O2 and
CO2 indicated moderate to excellent
agreement between the fifth and sixth minute of exercise at pressure
and during exercise 2 at the surface (kappa > 0.74, P < 0.05). Agreement was weaker for
O2 (kappa 0.53, P = 0.0595) and CO2 (kappa 0.69, P = 0.0265) during exercise 1 at the
surface, although the average difference was small. Overall, these
values indicate that the final minute of exercise represented
a steady-state condition.
Spirometry. At 2.8 ATA, FVC was 4.58 ± 1.22 liters, which was unchanged compared with surface values of 4.36 ± 0.96 liters (P = 0.23). FEV1 decreased from 3.58 ± 0.89 liters at the surface to 2.90 ± 0.66 liters at pressure (P <0.0001), and FEF25-75 decreased from 3.43 ± 1.14 to 2.11 ± 0.52 l/s (P < 0.0001). When FVC, FEV1, and FEF25-75 are expressed as a percent of predicted values, there were no significant differences between groups Y and O at 1 ATA or 2.8 ATA.
pH and PaCO2.
At 2.8 ATA, PaCO2 was significantly higher than at 1 ATA during rest (+1.8 Torr, P = 0.0059) and
exercise 1 (+4.2 Torr, P < 0.0001), with
the greatest difference during exercise 2 (+7.8 Torr,
P < 0.0001). At 1 ATA, PaCO2 dropped
significantly during exercise 2, but this decrease was
attenuated at 2.8 ATA (Table 2 and Fig.
1). Significant arterial hypercapnia was
not observed, with only three subjects having
PaCO2 > 45 Torr (maximum 45.4 Torr) during
exercise at 2.8 ATA.
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0.01 during rest (P = 0.0084) to 0.03 during exercise 2 (P > 0.0001).
PaCO2 and PETCO2.
PETCO2 overestimated
PaCO2 at 1 ATA during rest and exercise (Table 2 and
Fig. 2), although on average the
arterial-to-end-tidal difference
(PaCO2-PETCO2) was
small. At 2.8 ATA, PETCO2 underestimated PaCO2 during rest and, as at 1 ATA, overestimated it
during exercise. However, the degree to which
PETCO2 overestimated
PaCO2 during exercise was less at 2.8 ATA.
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9.0 and 11.8 Torr.
Furthermore, although the absolute
PaCO2-PETCO2 was
least at pressure, there was large intersubject variability at both 1 and 2.8 ATA. To further analyze the variability in
PETCO2 as an estimate of
PaCO2, Bland-Altman analysis was performed on
PaCO2-PETCO2 at 1 and 2.8 ATA separately for rest and exercise (Fig.
3), as well as for both conditions
combined. Results are reported as means (lower limit of agreement,
upper limit of agreement), where the limits of agreement are equal to
the mean ± 1.96 SD. During rest and exercise at 1 ATA,
PaCO2-PETCO2 was
3.73 (9.31, 1.85) (P < 0.0001) and 5.13 Torr
(10.92, 0.65) (P < 0.0001), respectively. During
rest and exercise at 2.8 ATA,
PaCO2-PETCO2 was
2.21 (2.04, 6.45) (P = 0.0002) and 2.46 Torr
(9.88, 4.95) (P = 0.0089), respectively.
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2.79 Torr (16.37,
10.79). On average,
PaCO2-PETCO2 was
closer to zero at 2.8 ATA during both rest and exercise. During rest, the variability was less at 2.8 ATA than at the surface. However, during exercise, the variability increased. Therefore, we conclude that
the reliability of PETCO2 as an estimate
of PaCO2 is imperfect under all conditions, but worse
during exercise at 2.8 ATA.
Alveolar and arterial O2. After correction for partial pressure of water vapor at 37°C, inspired PO2 (PIO2) was 112 Torr at 1 ATA and 383 Torr at 2.8 ATA (equivalent to inspired O2 fraction of 57% at 1 ATA). Accordingly, PaO2 and PAO2 were significantly higher at pressure (Table 2). PaO2/PAO2 was lower in group O on average by 0.04 (P = 0.013). After adjustment for age and work rate, PaO2/PAO2 was lower at pressure on average by 0.06 (P <0.0001). However, there was a significant interaction between work rate and pressure (P = 0.0002), such that the effect of pressure on PaO2/PAO2 depended on work rate and was greatest during rest. There was no functionally significant impairment of O2 exchange at 2.8 ATA, and O2 saturation exceeded 98% in all subjects.
Pulmonary ventilation and VDS.
Compared with surface values, E at pressure was
significantly decreased during both exercise 1 (2.6 l/min
BTPS, P = 0.0004) and exercise 2 (13.1 l/min BTPS, P < 0.0001), caused by
decrements in both Vf and VT (Table 2). In contrast, there
was a slight but significant increase in E at rest
of 1.06 l/min (P = 0.0192). A was
unchanged at pressure during rest and, similar to E, reduced during exercise (Fig. 4).
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Age effects.
In group O, VDS was higher on average by 0.089 liter (P = 0.018), and
PaO2/PAO2
was less on average by 0.04 (P = 0.013). After adjustment for work rate and pressure, groups Y and
O had no significant differences in the following variables:
PaCO2, PETCO2,
PaCO2-PETCO2, pH,
E, VT, Vf, A, and
VDS/VT.
Gender differences. Gender differences were not a primary outcome of this study, and, therefore, it was underpowered to detect a significant effect of gender while adjusting for age, work rate, and atmospheric pressure. A simple comparison (t-test) of VDS, VDS/VT, PaCO2, PETCO2, and PaCO2-PETCO2 revealed only slight differences in PaCO2 during exercise 2 at 1 ATA [28.90 ± 2.66 Torr (women), 33.24 ± 4.12 Torr (men), P = 0.014] and PETCO2 during exercise 2 at 1 ATA [32.66 ± 4.90 Torr (women), 38.42 ± 5.97 Torr (men), P = 0.032]. PaCO2-PETCO2 was similar in both groups during this same condition (P = 0.379).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Physiological VDS. This study at 18.3 m (gas density 3.1 g/l) reports the first measurements of physiological VDS during rest and exercise at depths <460 m (gas density 12.3 g/l). Even at this moderate depth, VDS significantly increased and caused significant changes in PaCO2, PETCO2, and the relationship between them. These changes were evident during both rest and exercise and were affected little by age.
In a similar study (47) performed at 47 and 66 ATA (gas densities 12.3 and 17.1 g/l), VDS (liters BTPS) was 0.64 at rest and 0.99 during heavy exercise at 66 ATA, with similar values at 47 ATA. Changes in VDS/VT closely followed changes in VDS in both studies. These results suggest a progressively increasing effect of pressure or gas density on VDS during rest and exercise that is present even at 2.8 ATA and reaches a maximum by 47 ATA. Because the direct effects of atmospheric pressure on human physiology are minimal at 2.8 ATA, the increase in VDS in our study is most likely due to the effects of increased gas density on the respiratory system. Physiological VDS, as measured by the Bohr equation, comprises all components of respiratory VDS-anatomical VDS (the volume of the conducting airways), lung units with ventilation-to-perfusion ratios (A/
) > 1, and lung units that are
ventilated but not perfused (A/ = 
).
Anatomical VDS or changes in
A/ distribution are the only
components of physiological VDS likely to contribute to the
elevation observed in this study. Intra-alveolar diffusion limitation
or a defect in CO2 transport, e.g., altered carbonic anhydrase activity (6, 7), could theoretically contribute to an increase in VD at extreme atmospheric pressure but
would not be expected to contribute to VDS at the
relatively modest pressure of 2.8 ATA. Hyperoxia and the Haldane effect
have also been reported to increase VDS by affecting
A/ mismatch.
Anatomic VDS is elevated by the effect of increased
gas density on airways resistance, which consequently favors a higher lung volume (18). End-inspiratory lung volume has been
shown to increase during maximal exercise from ~85% of vital
capacity to 90% of vital capacity at 3 ATA (18). In a
separate study, with an increase in end-inspiratory lung volume from
3.2 to 7.7 liters, anatomic VDS increased from 130 to 245 ml (49). By extrapolating the expected increase in
anatomic VDS on the basis of these data and an average FVC
at 1 ATA in this study of 4.48 liters BTPS, the
corresponding increase in anatomic VDS at 2.8 ATA would be <0.006 liter BTPS. This effect is not large enough to
account for >10% of the observed increase in physiological
VDS.
Hyperoxia has been shown to increase PaCO2 (32,
34) and VDS/VT (2, 34) in
patients with lung disease. Theoretically, elevated
PIO2 could alter VDS by its
effect on A/ matching, resulting in part from
the release of hypoxic pulmonary vasoconstriction and thereby
increasing the proportion of lung units with effective shunt
(A/ < 1). However, the effect of
hyperoxia on actual A/ distribution, as
measured by the multiple inert-gas elimination technique, is unclear
(52, 53), and in healthy subjects there is no significant
effect of hyperoxia on PaCO2 or
VDS/VT (3).
Additionally, the Haldane effect contributes to a small elevation in
measured VDS/VT in response to increased
PIO2 in hypoxemic patients (2, 17,
36). The Haldane effect describes the indirect relationship
between CO2 binding to hemoglobin and O2 saturation, whereby oxygenated blood at any
PCO2 has a lower CO2 content than
deoxygenated blood at the same tension. The importance of this effect
is directly related to the severity of the initial hypoxemia and
hypercapnia (20, 34, 36), and, whereas the increase in gas
density during diving simulates diffuse airway obstruction caused by
structural lung disease, divers are neither hypoxemic nor hypercapnic
at 1 ATA. On the basis of a nomogram developed by Lenfant
(34), the estimated change in PaCO2
during exercise 2 at 2.8 ATA due to the Haldane effect would
be <1 Torr.
The most likely mechanism of increased VDS in response to
hyperbaric exposure is a worsening of A/
mismatch. Changes in A/ matching are
reflected indirectly by measurements of O2 and
CO2 exchange, and dense-gas breathing has been shown to
decrease the alveolar-to-arterial O2 gradient
(PAO2-PaO2) while at the same time causing an increase in VDS/VT and
PaCO2 (39, 46, 47, 57). The detrimental
effect of gas density on A/ matching is
supported by studies utilizing the multiple inert-gas elimination technique, which assesses distributions of ventilation and perfusion independent of O2 or CO2 analysis
(9). A maldistribution of ventilation in response to
increased pressure would increase the proportion of lung units with
A/ > 1, therefore contributing to an
increase in physiological VDS. We, therefore, hypothesize that increased gas density accounts for the majority of the elevation in VDS at 2.8 ATA by its detrimental effect on
A/ mismatch.
Pulmonary ventilation.
Salzano et al. (47) report a bimodal ventilatory response
to exercise at 47 and 66 ATA that is similar to the findings of this
study at 2.8 ATA: increased E at rest, and decreased
E with heavier exercise. The decrease in
E during exercise at 2.8 ATA is caused by decrements
in both Vf and VT, although changes in VT were
only significant during exercise 2. A was
unchanged between 1 and 2.8 ATA at rest and decreased only with
exercise. The decrease in A during exercise is
caused by both the decrease in E and an increase in
VDS/VT, which is elevated predominantly because
of increased VDS. To explain these effects of atmospheric pressure on ventilation, we propose that increased VDS is
the primary perturbation that leads to a compensatory increase in E at rest or light exercise levels, but that
inadequate A results when the respiratory drive
inadequately compensates for the increased VDS during
heavier exercise.
E and A were
minimal at rest and profound during the heaviest exercise. The many
proposed mechanisms for a decreased ventilatory drive during exercise
at depth include 1) a conscious hypoventilation by trained
divers (16, 25, 27); 2) a diminished
ventilatory response to inhaled CO2 in certain subjects
(40), possibly secondary to an acquired adaptation in
divers (15); and 3) altered chemosensitivity to
CO2 as a result of increased pressure (25) or
the effects of increased partial pressures of O2 and
N2 (30).
PaCO2 during rest and exercise.
The reported effects of increased pressure or gas density on resting
PaCO2 are variable (46, 47, 50). In this
study, resting PaCO2 was normal but slightly higher at
2.8 ATA than at the surface (+1.8 Torr). However, at the surface,
PaCO2 was abnormally low (33.8 Torr) and pH was
slightly high (7.42), consistent with a mild respiratory alkalosis that
may have been due to hyperventilation. The phenomenon of
hyperventilation in naive subjects breathing on a mouthpiece has been
observed before in this laboratory, especially during rest; this effect
usually disappears with exercise. Because surface trials were always
performed first, the increase in resting PaCO2 at
pressure could simply represent a normalization of an abnormally low
surface value due to an increasing familiarity with the experimental
apparatus. However, both E and
VDS/VT were slightly higher during rest at 2.8 ATA, and CO2 was unchanged. In this
circumstance, the only variable that increases PaCO2
is the increase in VDS/VT.
E, consistent with a mild exercise-induced
acidemia. During exercise 2 at pressure, a further drop in
pH and increase in PaCO2 are consistent with the
development of a respiratory acidosis superimposed on the underlying
metabolic acidemia. Furthermore, a decrease in E and
increase in VDS/VT both appear to contribute to
the increase in PaCO2 during exercise. By calculating
the expected value of PaCO2 if
VDS/VT had remained unchanged, 42% of the
increase in PaCO2 during exercise 2 at 2.8 ATA (3.3 of 7.8 Torr) is explained by the decrease in
E; the remaining difference is attributed to the
increase in VDS/VT.
PaCO2-PETCO2.
PETCO2 is a common, noninvasive estimate
of PaCO2, the limitations of which are well known for
rest and exercise at 1 ATA across a range of ages (22, 44, 55,
56). During spontaneous breathing at rest, the alveolar
VDS fraction usually causes
PETCO2 to slightly underestimate true
alveolar PCO2
(PACO2), and therefore PaCO2, in both younger and older subjects
(56), producing a positive
PaCO2-PETCO2.
During exercise, PETCO2 generally
overestimates PaCO2 because of several factors,
including: 1) an increase in average
PAO2 due to increased
VT, which has the effect of diminishing the contribution of
alveolar VDS, 2) increased cardiac output, which
increases pulmonary blood flow and lowers the number of alveoli with
high A/, thereby increasing
PETCO2, and 3) increased mixed-venous PCO2, which, during the course of
exhalation, can cause a progressive rise in PaCO2 and
hence PETCO2 (13). With increasing age, PETCO2 during exercise is
closer to PaCO2 than it is in exercising younger
subjects (56), probably because of the increase in
VDS with age. The validity of
PETCO2 as an estimate of
PaCO2 under hyperbaric conditions has never previously been assessed.
8.5 to 9.4 Torr) when
PaCO2 was also at a minimum (20.8 to 18.5 Torr). As
discussed above, we suspect that the observed modest hyperventilation during rest at the surface was a product of unfamiliarity with the
experimental setup that may have lessened during pressure trials.
Therefore, we can make no conclusions about the effect of hyperbaric
exposure on
PaCO2-PETCO2
during rest.
PaCO2-PETCO2
during exercise at 1 ATA was consistent with previously published
values (23, 55), becoming more negative compared with
resting values as PETCO2 rose and
PaCO2 decreased. At 2.8 ATA,
PaCO2-PETCO2 was
higher than at the surface. Changes in
PaCO2-PETCO2 at
pressure can be explained by the direct relationship between
PaCO2-PETCO2 and
VDS/VT (Fig. 8). Just as the rise in PETCO2 during exercise is partly explained
by the accompanying decrease in VDS/VT, the
elevation of VDS/VT at pressure can be expected
to lower PETCO2. Therefore, on average the
increase in VDS/VT at pressure reduced the
magnitude by which PETCO2 overestimated PaCO2 during exercise.
Interestingly, increased pressure altered the relationship between
PaCO2-PETCO2 and
VDS/VT, such that changes in
VDS/VT had more of an effect at 2.8 ATA,
especially during rest (Fig. 6). This phenomenon is consistent
with an increase in A/ mismatch at higher
gas densities, with a greater proportion of lung units with
A/ > 1 contributing to
VDS/VT. The slopes converge during exercise, which may reflect the decreasing contribution of
VDS/VT to
PaCO2-PETCO2
relative to the effect of the increasing mixed-venous PCO2.
Although it is tempting to conclude that
PETCO2 more accurately reflects
PaCO2 under hyperbaric conditions, the wide
variability of
PaCO2-PETCO2 makes
capnography an imprecise way to assess hypercapnia at depth. Large
differences between PaCO2 and
PETCO2 existed even at the surface, and at
2.8 ATA, PETCO2 still overestimated
PaCO2 by 9-11 Torr in two subjects. Furthermore,
elevated PETCO2 did not predict arterial
hypercapnia. In the two instances of
PETCO2 greater than 50 Torr,
PaCO2 did not exceed 45 Torr. These results were
obtained in the setting of a relatively modest increase in gas density
during moderate exercise; under more extreme conditions, the
relationship between PETCO2 and
PaCO2 may be even less certain. However, it is also
important to emphasize that, in many diving studies, extreme elevations
of PETCO2 have been strongly correlated with symptoms consistent with hypercapnia (29, 37, 40), even though PaCO2 was not directly measured. Further
studies in divers to correlate PETCO2 with
PaCO2 would be useful, given the demonstrated
variability of PETCO2 under the conditions
that are most relevant to working divers, i.e., exercise.
O2 and
CO2.
For a given work rate, O2 tended to be
higher at pressure than at 1 ATA and CO2
tended to be lower, although these differences were small even at the
highest work rates.
O2 may have been
elevated by the increased work of breathing at pressure, whereas
CO2 may have been lowered by
hypoventilation and the consequent accumulation of CO2. The
conclusions of this study would not be altered by small perturbations
of O2 and
CO2.
Differences between older and younger subjects. As expected, VDS was slightly higher in group O during all conditions. The higher VDS was not associated with significantly higher values of VDS/VT or PaCO2 for group O during exercise or at pressure, nor was there a greater relative increase in VDS at pressure. PaCO2-PETCO2 was similar in both groups under all conditions. The only other difference between groups was a slight but functionally insignificant decrease in PaO2/PAO2 in group O. The excellent performance of group O on every other measure of lung function and exercise ability make it unlikely that older divers in good health would experience significantly greater increases in PaCO2 at 2.8 ATA, or that PETCO2 would be less accurate in this particular age group.
In conclusion, rather than being an isolated phenomenon of extreme hyperbaric exposure, changes in physiological VDS were apparent during both rest and exercise even at 2.8 ATA. The increase in VDS most likely reflects changes inA/ matching due to the increased gas density,
even though the increase in gas density was not large enough to cause
dyspnea or discomfort. Because of an inadequate ventilatory
compensation for an increase in physiological VDS,
PaCO2 increased during rest and exercise. Significant
arterial hypercapnia did not occur, even during the heaviest exercise.
The increase in VDS/VT at 2.8 ATA contributed
to a decrease in the expected elevation of
PETCO2 above PaCO2 during
exercise. Consequently, the absolute
PaCO2-PETCO2
difference was less during exercise at 2.8 ATA. However, large
intersubject variability at both 1 and 2.8 ATA makes
PETCO2 an imperfect estimate of
PaCO2 for monitoring individual divers.
Finally, this study in a dry hyperbaric chamber does not support the
hypothesis that older divers in good physical condition with no
underlying pulmonary or cardiovascular disease are at any increased
risk of respiratory impairment during moderate exercise at 2.8 ATA.
| |
ACKNOWLEDGEMENTS |
|---|
The authors gratefully acknowledge the expert technical contributions of Eric Alford, Aaron Walker, and Eric Schinazi. We also express profound appreciation for the commitment and effort of our 20 subjects, without whom the study would not have been possible.
| |
FOOTNOTES |
|---|
This project was funded by the Divers Alert Network.
Address for reprint requests and other correspondence: R. Moon, Dept. of Anesthesiology, Box 3094, Duke Univ. Medical Center, Durham, NC 27710 (E-mail: moon0002{at}mc.duke.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
First published October 11, 2002;10.1152/japplphysiol.00367.2002
Received 25 April 2002; accepted in final form 7 October 2002.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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