1. health and fitness
2. exercise

Ventilation and Gas Exchange During
Sleep and Exercise in Severe COPD*
Eithne Mulloy, MR; and Walter T McNicholas, MD
Ventilation and gas exchange were studied during
sleep and incremental treadmill exercise in 19 patients
with severe stable COPD with the primary aim of
comparing the pathophysiology of oxygen desatura¬
tion in the two conditions. A secondary aim was to de¬
termine whether exercise studies could aid in the
prediction of sleep desaturation. Full polysomnography was used, and ventilation, arterial oxygen satura¬
tion (SaC>2), and transcutaneous PCO2 (PtcC02) were
monitored continuously during sleep. No patient had
significant sleep apnea. Mean (SD) FEVi was 32 (9.1)%
predicted, Pa02 was 71.2 (12.4) mm Hg, and PaC02
was 44.5 (4.6) mm Hg. SaC>2 fell twice as much during
sleep as during maximum exercise: 13.1 (8.9) vs 6.0
(3.6)% (p<0.001). The mean sleep and exercise SaC>2?
and minimum sleep and exercise SaC>2 were well cor¬
related on linear regression (r=0.81 and 0.78, respec¬
tively, p<0.001), but on multiple regression analysis,
awake Pa02 was a better predictor of sleep desatura¬
tion than was exercise desaturation. The 12 major desaturators (minimum sleep SaC>2 <85%) had twice as
great a fall in exercise Sa(>2 as the 7 minor desaturators (3.6±2.8 vs 7.4±3.3%, p<0.05). The major desat-
"Datierits with COPD develop varying degrees of ox-
ygen desaturation during sleep,1"4 which may con¬
tribute to the development of cor pulmonale5 and
nocturnal death.6 Patients with COPD also frequently
desaturate during exercise.7 Hemodynamic variables
have been studied during sleep and exercise in
COPD,89 but potential relationships between oxygen
desaturation during sleep and exercise have not been
in detail. A recent preliminary report from
reported
this department,10 in which simple overnight and ex¬
-*¦
ercise oximetry were
performed in hopitalized patients
from an acute exacerbation of COPD,
convalescing
demonstrated greater nocturnal than exercise desatu¬
ration. However, the lack of sleep staging or measure¬
ment of ventilation cast doubt on the significance of
these findings. Furthermore, patients with interstitial
have been shown to desaturate more
lung disease
during exercise than sleep,11 which indicates that sleep
*From the Department of Respiratory Medicine and the Respira¬
tory Sleep Laboratory,
University College Dublin, St. Vincent's
Ireland.
Hospital, Dublin,
received
Manuscript
February 8, 1995; revision accepted SeptemReprint requests: Dr. McNicholas, St. Vincent's Hospital, Elm Park,
Dublin 4, Ireland.
urators also had a greater fall in estimated
sleep Pa02:
19.8 (5.1) vs 6.4 (7.1) mm Hg (p<0.01), which suggests
that their greater sleep desaturation is not simply due
to their
position on the steep portion of the oxyhemoglobin dissociation curve. The rise in PtcC02 during
sleep was similar among major and minor desaturators: 7.5 (2.9) vs 5.8 (3.7) mm Hg (p=NS), suggesting
that all patients had a similar degree of hypoventilation
during sleep, and that the greater fall in Sa(>2 and es¬
timated PaC>2 among some patients was secondary to
other factors such as increased ventilation-perfusion
(CHEST 1996; 109:387-94)
mismatching.
mass index; PtcC02=transcutaneous carbon
BMI=body
dioxide tension; Sa02=arterial oxygen saturation; Ve
max=maximum minute ventilation during exercise; V02
max=maximum oxygen uptake during exercise; V/Q ven¬
tilation-perfusion
Key words: COPD; exercise; gas exchange; sleep; ventila¬
tion
and exercise may have different effects on gas ex¬
change in different forms of chronic lung disease.
The primary aim of the present study was to com¬
pare ventilation and gas exchange during sleep and
exercise in COPD, and to assess whether a detailed
of ventilation and gas exchange during
knowledge
and
in the same patient population
exercise
sleep
would give insight into the pathophysiology of these
The mechanisms that lead to oxygen desatu¬
changes.
ration during sleep and exercise in COPD likely differ.
During sleep, important mechanisms are decreased
drive causing hypoventilation, and changes
ventilatory
in ventilation-perfusion (V/Q relationships caused by
decreased functional residual capacity and increased
airflow obstruction.12"14 During exercise, the normal
increase in ventilation and in lung volumes
physiologic
is limited in COPD because of the effects of increased
airflow resistance, inadequate ventilatory response,
and lack of reduction in dead-space. These factors
combine to cause relative hypoventilation and V/Q
disturbances, leading to hypoxemia in some pa¬
tients.7'15'16
A secondary aim of the present study was to deter¬
mine whether exercise studies could aid in the preCHEST /109 / 2 / FEBRUARY, 1996
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387
diction of nocturnal desaturation in COPD. While
PaO£ correlates well with nocturnal arterial
daytime saturation
(Sa02) in COPD,31'"19 many pa¬
oxygen
tients with mild daytime hypoxemia develop unex¬
nocturnal oxygen desaturation.4
pected
We studied a group of outpatients with severe but
stable COPD, in whom the principle inclusion crite¬
rion was FEVi less than 50% predicted. A specific
of hypoxemia was purposely not included be¬
degree
cause we wished to study patients with varying degrees
of hypoxemia and hypercapnia. Some reports have
suggested that patients with relatively normal arterial
blood gas values despite severe airflow obstruction
(so-called "pink puffers") may be more likely to
desaturate during exercise,20 similar to patients with
interstitial lung disease,11 whereas patients with more
marked hypoxemia, hypercapnia, and cor pulmonale
(so-called "blue bloaters") appear more likely to de-
saturate
during sleep.2"5'19
Materials
and
equations).22
Exercise Studies
Methods
Patient Selection
Nineteen consecutive
ambulatory patients (13 male, 6 female)
attending the outpatient respiratory clinic who fulfilled the entry
criteria were enrolled. All had severe, stable COPD, fulfilling the
American Thoracic Society diagnostic criteria.21 Their FEVi was
less than 50% predicted, and FEVi/FVC ratio was less than 60%.
All were current or previous cigarette smokers, and none had sus¬
tained an exacerbation of their disease for at least 6 weeks prior to
enrollment. Patients with a clinical history suggestive of sleep ap¬
nea, such as loud snoring or daytime sleepiness, were excluded, as
were patients with ischemic heart disease. All patients had been
regular attenders at our outpatient respiratory clinic for at least 1
year, and all patients who fulfilled the entry criteria were asked to
participate. The patients gave informed consent to the study, which
was approved by the Hospital Ethics Committee.
Table
The pulmonary function testing and exercise testing were
performed in the early afternoon, after a light lunch. ^-Agonist
therapy was omitted for at least 6 h and theophylline preparations
were omitted during the entire study day. All but two patients were
nonsmokers at the time of the study, and these subjects were asked
to refrain from smoking for at least 4 h before exercise testing. The
subjects were allowed to rest for 30 min after arrival, then arterial
blood gas samples were drawn from the radial artery and analyzed
immediately.
Pulmonary Function Studies
Pulmonary function tests were measured (with a P.K. Morgan
computerized T.T. Autolink and Body Box system; P.K. Morgan
Ltd; Rainham, England). Spirometry was performed before and 15
min after inhalation of 400 pg of salbutamol. Single-breath carbon
monoxide gas transfer was performed and lung volumes were
measured by both helium dilution and whole body plethysmography techniques. Three subjects were unable to perform the body
plethysmographic measurements due to claustrophobia or dyspnea.
The data were analyzed using both absolute values and percent of
normal predicted values (European Coal and Steel Community
Incremental treadmill exercise testing was performed immedi¬
ately following the pulmonary function testing, using a computer¬
ized exercise system (Morgan). Subjects wore a noseclip and
breathed through a mouthpiece connected to a two-way valve, such
that room air was inspired, and the exhaled gases were collected in
a mixing chamber and analyzed at 10-s intervals by the computer¬
ized system. The gas analyzers were calibrated against gas mixtures
of a known concentration (5% CO2, 12% O2) prior to each test.
Maximum oxygen uptake (V02 max) and minute ventilation (Ve
max) represent the highest values achieved for each of these
parameters during exercise, and these were expressed both as ab¬
solute values and percentage of normal predicted values.23 The
patients were encouraged to exercise to exhaustion, using the
modified protocol of Naughton et al,24 which allows for a gradual
increase in exercise intensity, suitable for patients with respiratory
impairment. Exercise commenced with a zero gradient and tread-
1.Anthropometries Pulmonary Function, Sleep, and Exercise Data*
All Patients
Age,yr
BMI, kg/m2
Pa02, mm Hg
PaC02, mm Hg
FEVi, % predicted
TLC, % predicted
RV, % predicted
Deo, % predicted
(n=19)
64.8 (5.2)
24.3 (3.4)
71.2 (12.4)
44.5 (4.6)
32.4 (9.1)
117(14.1)
200 (39.4)
51.3(10.4)
287 (71)
44 (25.6)
34.8 (10.1)
27.2 (6.6)
736 (201)
76 (41.1)
337(175)
Minor Sleep
Desaturators
(n=7)
61.7 (5.3)
22.6 (2.6)
83.8 (4.0)
41.0(1.4)
30.7 (9.7)
Major Sleep
Desaturators
(n=12)
66.6 (4.5)f
25.3 (3.5)
63.9 (9.3)*
46.6 (4.7)*
33.4 (9.0)
112 (10.5)
125(16.5)
193 (40.2)
213(38.1)
52.7 (7.7)
49.6(13.9)
290 (87)
Total sleep time, min
285 (65)
REM sleep, min
50 (35.7)
40 (18.2)
31.9 (6.2)
V02 max, % predicted
36.7(11.8)
Ve max, % predicted
27.1 (8.9)
27.2 (5.2)
Vco2 max, mL/min
780(207)
709(207)
Maximum W
67 (19.6)
81 (49.7)
Exercise duration, s
325 (124)
345(204)
*TLC=total lung capacity; RV=residual volume; Dco=diffusing capacity of carbon monoxide; Vco2 max=maximum carbon dioxide production.
fp<0.05.
\ p<0.001.
^p<0.01. The p values refer to differences between major and minor desaturators.
388
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Clinical Investigations
Table 2.SaC>2, PtcC02, and Estimated Pa02 During Sleep and Exercise
Presleep Sa02, %
Mean sleep Sa02> %
Minimum sleep SaC>2, %
Fall in sleep Sa02, %
Presleep PtcCC>2, mm Hg
Mean sleep PtcC02
Maximum sleep PtcC02
Rise in sleep PtcC02
Presleep Pa02, mm Hg
Minimum sleep PaC>2
Fall in sleep PaC>2
Preexercise SaC>2, %
Minimum exercise Sa02, %
Fall in exercise SaC>2, %
All Patients
Minor Sleep
Desaturators
(n=19)
92.1 (4.0)
88.6 (7.5)
79(11.9)
13.1 (8.9)
54.1 (6.3)
57 (6.4)
61.2 (8.0)
7.1 (3.2)
67.3 (9.1)
51.4 (13.0)
15.9 (9.2)
91.2 (4.4)
85.2 (7.0)
6.0 (3.6)
(n=7)
94.3(1.4)
93.9 (0.9)
89.3 (2.5)
5.0 (3.2)
50.3 (3.3)
52.2 (3.8)
56.1 (6.4)
5.8 (3.7)
71.8 (5.7)
65.4 (4.2)
6.4 (7.1)
93.5 (1.6)
89.9 (2.4)
3.6 (2.8)
Major Sleep
Desaturators
(n=12)
90.9 (4.5)
85.6 (8.0)*
73(11.1)*
17.9 (7.5)f
56.2(7.1)
59.4 (6.3)*
63.7 (7.6)
7.5 (2.9)
64.1 (10.0)
44.3(10.1)*
19.8(5.1)f
89.9 (5.0)*
82.5 (7.5)*
7.4 (3.3)*
*p<0.001.
fp<0.01.
*p<0.05. The p values refer to differences between major and minor desaturators.
(mph) for 2 min, the workload
15° elevation over 20 min. All subjects terminated the exercise be¬
cause of dyspnea. SaC>2 was measured continuously by a pulse
oximeter (Ohmeda Biox 3700) with ear electrode (Ohmeda Inc;
Boulder, Colo),25 and connected on-line to the computer. The
preexercise SaC>2 was taken as the stable, standing, SaC>2 for at least
30 s immediately prior to commencing exercise. The mean SaC>2 was
mill
speed of 1
mile per hour
increasing at 2-min intervals to a potential maximum of 3 mph at
taken as the mean of all the measurements taken from the onset of
exercise to termination of exercise. The lowest SaC>2 reached dur¬
ing exercise was noted, and the fall in exercise SaC>2 was taken as
the difference between this value and the preexercise SaC>2. This is
given as a minus value in patients whose SaC>2 rose during exercise.
Sleep Studies
These
were
performed
on
the
night immediately following
exercise testing. All patients had spent a previous acclimatization
usual bedtime med¬
night in the sleep laboratory. They took their
11 pm as
ication (except
lights-out was as close tomaximum
and the patients were allowed to sleep until a
theophylline);
of 8
Standard polysomnographic techniques were used,26 and
the ECG was recorded from a single precordial lead. Respiration
was measured using a respiratory inductance plethysmograph (Respitrace; Ambulatory Monitoring Inc; Ardsley, NY) that was
calibrated using the isovolume technique.27 The above variables
were recorded continuously on a polygraph recorder (model 78D;
Grass Instruments Inc; Quincy, Mass), and sleep was staged man¬
criteria.26 The number
ually in 30-s epochs accordingofto standard for
of apneas (complete cessation breathing more than 10 s) and
to less than 50% of preced¬
hypopneas (abrupt fall in tidal volume
in
of at least 4%) were re¬
a
fall
SaC>2
levels,
by
accompanied
ing
corded. SaC>2 was recorded continuously using the same oximeter
as for the exercise studies, with an ear electrode. Transcutaneous
CO2 (PtcC02) was measured continuously during sleep by a tran¬
with a heated
possible,
am.
capnometer (Hewlett-Packard 47210A)
to the skin of the forearm (Hewlett Packard Inc;
Waltham, Mass). This device gives an accurate indication of grad¬
ual changes in arterial PCO2, but the PtcCC>2 has been reported to
scutaneous
sensor
affixed
be approximately 4 mm Hg higher than the arterial PCO2,28 a find¬
ing confirmed with our capnometer. There is also a delay in equil¬
ibration between the PtcC02 and the PaC0228 However, we found
that episodes of hypoventilation lasting as little as 30 s were suffi¬
cient to show a rise in PtcCC>2 a few minutes later, the delay
reflecting the time lag between change in PaCC>2 and subsequent
change in PteCC>2. Thus, we believed that this capnometer was
sufficiently accurate for monitoring changes in PaCC>2 during
sleep-related episodes of oxygen desaturation, but was not suitable
for exercise studies. Satisfactory readings of PtcCC>2 were obtained
in 15 patients. Both the SaC>2 and PtcC02 were continuously
recorded on an ink-writing paper recorder that was synchronized
with the recorder (Grass). The data were analyzed by averaging the
and low SaC>2 and PtcCC>2 for each 2-min period. The first 5
high
min after entering each sleep stage were omitted from the analysis
of PtcC02 because of the delay in equilibration of PtcCC>2 and
PaC0228
Presleep SaC>2 was defined as the mean of the stable, recumbent
Sa02 for 20 min prior to sleep onset. Mean SaC>2 was taken as the
mean Sa02 from the first onset of sleep (lasting at least three ep¬
ochs) until final awakening in the morning, including intervening
periods of wakefulness. The mean SaC>2 for each stage of sleep was
also calculated. The minimum or lowest Sa02 reached for at least
30 s during sleep was noted, and the fall in SaC>2 was calculated as
the difference between this value and presleep SaC>2. Similar
methods were used to analyze the Ptcco2 data.
The patients were divided into major and minor nocturnal
desaturators based on the criteria that major desaturators had an
SaC>2 during sleep of less than 90% for at least 5 min, reaching a
minimum Sa02 of at least 85%, while all the other patients were
classified as minor desaturators (Tables 1 and 2). This definition was
chosen to facilitate comparison with other studies of nocturnal ox¬
ygen desaturation in COPD4,8 that used similar criteria.
Statistical Analysis
The data are presented as mean values ±1 SD. A p value of 0.05
or less is taken as significant. Statistical methods used included
simple regression, multiple linear, and forward stepwise regression
as appropriate. Means of continuous variables were compared by
the Student's t test or Wilcoxon signed rank test, and categorical data
were analyzed using the x2 test. A computerized statistics software
package (Statistica TM) was used for analysis of the data.
Results
All 19 patients completed the study, and all achieved
least 10 min of rapid eye movement (REM) sleep.
Their anthropometric, blood gas, pulmonary function,
sleep, and exercise data are given in Tables 1 and 2.
at
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389
without invasive measurements of gas exchange during
variable nature of respiration during REM
sleep. The
with possible variations in the respiratory quo¬
sleep,
tient during
and the larger body
stores of CO2 also make calculations based on the
alveolar air equation difficult to interpret. Despite
these difficulties, we hoped that the present study
would provide some useful data on this subject, as we
obtained an indirect measurement of PaC02 by con¬
tinuous monitoring of PtcC02, unlike previous studies
that relied on intermittent blood gas sampling.1'213,14
The continuous monitoring of PtcC02 helped us to
estimate Pa02 during sleep from the Sa02 trace, since
we could make an allowance for the effect of a chang¬
ing PaC02 on the oxyhemoglobin dissociation curve.
These measurements represent an estimate only, as
there are delays between the equilibration of PtcC02
and PaC02, as discussed above. Using this indirect
method, we found a somewhat larger fall in Pa02 and
rise in PtcC02 during sleep than some other studies of
COPD patients in whom arterial blood gases were
sampled intermittently,1314 but our findings are simi¬
lar to those of Koo et al.1 The maximum rise in PaC02
was 45% of the fall in Pa02 (Table 2), which is similar
to other reports.114
The continuous monitoring of PtcC02 showed that,
nature, the falls in Sa02 were
despite their transient
in
a
rise
PtcC02 a few minutes later,
accompanied by
the delay reflecting the time lag between change in
PaC02 and subsequent change in PtcC02.28 The
greater body storage capacity for CO2 did not seem to
prevent these transient rises in PtcC02. REM sleep, in
particular, was frequently characterized by irregular,
low tidal volume respiration on the record (Respitrace), and a high PtcC02 (Table 3). These observa¬
tions support hypoventilation as one of the major
causes of nocturnal desaturation in COPD, particularly
the similar rise in
during REM sleep. inHowever,
PtcC02 during sleep the major and minor desatu¬
rators suggests that both groups had a similar degree
of hypoventilation, and that factors such as lower po¬
sition on the oxyhemoglobin dissociation curve and/or
greater degrees of V/Q mismatching were responsible
for the greater degree of desaturation among major
desaturators.
As in other studies,317"19 we found that daytime
Pa02 correlates well with mean nocturnal Sa02, which
initially suggests that nocturnalofdesaturation may be
related to the presleep position hypoxemic patients
on the steeper portion of the oxyhemoglobin curve.
However, the patients who were major nocturnal de¬
saturators had a threefold greater fall in estimated
sleep Pa02 than the minor desaturators. We recognize
that the estimated Pa02 is not a precise measurement,
but the magnitude of difference in estimated Pa02
between major and minor desaturators strongly sup¬
hypoventilation,3'13
ports a real difference in this variable. This finding
suggests that the presleep position on the oxyhemo¬
globin dissociation curve was not the major determi¬
nant of the extent of O2 desaturation during sleep in
these subjects, since if this were the case, the fall in
calculated Pa02 should have been the same irrespec¬
tive of the Sa02. The much larger fall in estimated
Pa02 among the major desaturators, in conjunction
with the similar rise in PtcC02 in both patient groups,
supports the presence of gas exchange abnormalities
such as V/Q disturbances as a major cause ofthe excess
oxygen desaturation during sleep in major desatura¬
tors.
Numerous studies have found that patients with
awake hypercapnia are more likely to have nocturnal
oxygen desaturation,2"519 and we also found that all of
our hypercapnic patients had major nocturnal desatu¬
ration, despite similar pulmonary function to the normocapnics. However, we found that awake PaC02 is
not an independent predictor of nocturnal desatura¬
tion, which contrasts with the findings of some other
reports.17,19 A possible explanation for this discrepancy
is that, unlike these studies,17,19 we performed full
and respiratory monitoring on all
polysomnography
our patients, and were thus able to exclude apneic
events among all our patients, and to be confident of
sleep status. MacKeon et al18 also found that daytime
PaC02 was not an independent predictor of sleep
Sa02- There was a significant relationship between
PaC02 and the rise in sleep PtcC02 on sim¬
daytime
linear
regression analysis, but, as can be seen in
ple
the
Figure 2, relationship was weak, with a wide scat¬
ter of the data. We found that there was no significant
correlation on multiple regression analysis between
variables and the rise in sleep PtcC02 and we
daytime
also found a similar rise in PtcC02 during sleep among
both normocapnic and hypercapnic patients. These
findings suggest that there inis a similar degree of
hypoventilation during sleep all patients, regardless
of PaC02, secondary to the withdrawal of the wakefulness drive to breathe,33 and that the greater fall in
Sa02 during sleep among hypercapnic patients may be
due to worsening gas exchange abnormalities in addi¬
tion to their more marked baseline hypoxemia.
All except two of our patients desaturated during
exercise, and 14 of the total 19 patients had a fall in
exercise Sa02 greater than 5%. This represents a more
incidence of oxygen desaturation during ex¬
frequent
ercise in patients with COPD than reported in other
studies,8' and may be due to either a different patient
or to the fact that we use a treadmill rather
population
than cycle ergometer.35 Early studies of exercise
in COPD proposed the theory that
pathophysiology
with
normocapnic respiratory failure had
patients
greater impairment of exercise ability and were more
likely to desaturate during exercise than patients with
CHEST /109 / 2 / FEBRUARY, 1996
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393
Table 4.Multiple Linear and Stepwise Regression Analysis of Sleep and Exercise Sa02*
Independent
Dependent variable: mean sleep SaC>2
Pa02
Constant
SE of estimate=4.17,
Regression
Partial r2
Variable
Age
0.69
0.045
37.7
2.7
Coefficient
SE
.00002
12
4.34
0.45
-18.89
1.62
0.26
40.18
0001
8.12
-0.36
0.53
1.05
-147.7
2.02
0.21
0.29
0.32
50.17
-6.07
0.31
-0.32
177.55
2.07
0.21
51.33
3.91
0.59
33.73
0.81
0.39
15.44
multiple correlation coefficient (r)=0.89, adjusted 1^=0.7
Dependent variable: minimum sleep Sa02
Pa02 0.662
FEVi
Lowest E
Sa02
Constant
SE of estimate=5.21,
0.054
0.056
Age 0.067
Pa02 0.551
FEVi 0.057
0.057
multiple r=0.87, adjusted r^O.64
Dependent variable: lowest exercise SaC>2
Pa02
05
06
07
multiple r=0.93, adjusted r^O.81
Dependent variable: fall in sleep SaC>2
Lowest E Sa02
Constant
SE of estimate=5.33,
33.27
4.74
4.14
3.94
0.568
BMI 0.053
0005
12
15
20.91
2.82
2.34
22.37
2.23
0002
15
Constant
SE of estimate=4.60,
0.3
multiple r=0.79, adjusted r^O.57
*Based on the findings from simple linear regression; age, BMI, percent predicted FEVi, daytime PaC>2, and PaCC>2 were entered into the multiple
regression analyses. Lowest exercise (E) SaC>2 was then entered into the regression analysis, with little change in the multiple correlation coefficients.
For the sake of brevity, only variables with a p value of 0.15 or less are included in the table.
puffer presentation of COPD with marked hyperin¬ Hg; p<0.001).
flation and severe airflow obstruction (mean FEVi,
There was only a weak correlation on simple linear
35% predicted), but relatively normal awake resting
regression analysis between the daytime PaC02 and
arterial blood gas values (mean Pa02, 83 mm Hg and
the rise in sleep PtcC02 (r=0.5, p<0.05) (Fig 2). Fur¬
PaC02, 40 mm Hg). However, although the hyperthermore, there was no significant correlation between
capnic patients (PaC02 >45 mm Hg) showed the the rise in PtcC02 and any daytime variable (including
PaC02) on multiple regression analysis. A particularly
greatest degree of desaturation during sleep, these
patients were also the greatest desaturators during ex¬ interesting finding ofthe present study was that the rise
ercise.
in PtcC02 during sleep was similar in the 7 hypercap¬
nic (PaC02 >45 mm Hg) and 12 normocapnic (PaC02
Factors Predicting Changes in Sleep Gas Exchange
<45 mm Hg) patients at 7.52 (3.7) and 6.3 (2.8) mm
Using simple linear regression analysis, daytime Hg, respectively.
Pa02 correlated significantly with the mean (r=0.83,
The continuous measurement of PtcC02
p<0.001), minimum (r=0.81, p<0.001), and fall in sleep sleep allowed us to estimate the Pa02 from theduring
Sa02
Sa02 (r=-0.74, p<0.001), similar to previous re¬
the standard oxyhemoglobin dissociation
tracing
using
ports.3^"9 Daytime arterial Pco2 also correlated signif¬ curve, since we could correct for changes in PCO2. The
icantly with the mean (r=-0.67, p<0.01), minimum
(r=-0.6, p<0.01), and fall in sleep Sa02 (r=0.54,
p<0.05). However, using multiple stepwise regression EE
analysis, Pa02 was the only variable with significant
with sleep Sa02 variables
independentandcorrelations
8
(p<0.001), neither awake PaC02 nor exercise de- £E
saturation were independent predictors of sleep Sa02
|r .S, p<CK05|
a
(Table 4). Daytime Pa02 accounted for 69% of the
in mean sleep Sa02 as compared with only
variability
1.5% for PaC02- Therefore, the significant correlation
Rise in Sleep PtcC02 (mmHg)
of PaC02 with sleep Sa02 on simple regression anal¬
Figure
2.
Correlation
PaC02 with the maximum rise
ysis likely reflects the fact that the hypercapnic patients in sleep PtcCC>2. Despiteofthedaytime
statistically
significant correlation, the
were more hypoxemie than the normocapnic patients
extent of the rise in sleep PtcCC>2 cannot be inferred from the level
(daytime Pa02, 58 mm Hg, as compared with 79 mm of the daytime PaCC>2.
CN
9
=
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391
major O2 desaturators had a substantially greater fall in
estimated Pa02 during sleep than the minor desatu¬
rators (Table 2), which suggests that the greater fall in
Sa02 among major desaturators is not simply due to
this group being on the steep portion of the oxyhemoaverage maximum fall in
globin dissociation curve. Thewas
more than twice the
estimated Pa02 during sleep
maximum rise in
PtcC02 (Table 2).
Predicting Exercise Desaturation
The major sleep desaturators had twice as great a fall
in exercise Sa02 as the minor sleep desaturators (Ta¬
ble 2), although the V02 max and Ve max were similar
in both groups. The hypercapnic patients also had
twice as large a fall in exercise Sa02 (8.9±2.5 vs
4.4±3.1%, p<0.01) despite similar exercise tolerance
to the normocapnic patients. However, the hypercap¬
nic patients also had a lower starting Sa02 than the
normocapnic patients (88±5.8 vs 93±1.7%, p<0.05).
On multiple stepwise regression analysis, resting Pa02
was the only variable that significantly correlated with
exercise desaturation, while PaC02, pulmonary func¬
BMI
not
to exercise desat¬
Factors
tion, age, and
uration
were
related
(Table 4).
Discussion
The present study represents the first report (to our
sleep
knowledge) usinganddetailed measurements ofcontin¬
stage, ventilation, gas exchange, including
uous PtcC02 monitoring, that compares gas exchange
in patients with COPD. The
during sleep and exercise
major findings were as follows: (1) Sa02 fell twice as
much during sleep as during maximal exercise; (2)
but
sleep and exercise Sa02 awere well correlated,
resting awake Pa02 was better predictor of sleep
desaturation than was exercise desaturation; and (3)
awake PaC02 was not an independent predictor of
nocturnal desaturation.
The finding that Sa02 fell more than twice as much
during sleep than during maximal exercise contrasts
with the findings in patients with interstitial lung dis¬
ease.11 The greater O2 desaturation during sleep sup¬
ports the findings of Shepard and coworkers,9 who, in
addition, found that in patients with COPD, sleep was
associated with a greater physiologic stress on the cor¬
onary circulation to maintain myocardial oxygen de¬
was exercise. This impaired oxygen delivery
livery than
in the nocturnal arrhythmias29 and the
a
be
factor
may
nocturnal
among
reported
higher with death rate6 previouslysince
the level of
COPD, particularly
patients
exercise achieved was much greater than the patients
would normally reach during daily activities. Nocturnal
oxygen desaturation also appears to be important in the
of pulmonary hypertension, even in the
development
absence of significant awake hypoxemia.30
The present findings of significant correlation be¬
392
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sleep and exercise Sa02 differ from those of
Fletcher and coworkers,8 who failed to find a signifi¬
cant correlation between these variables. However,
their study was principally directed at examining
hemodynamic
relationships during sleep and exercise
in COPD, and only brief mention is made in their re¬
port of the relationship between sleep and exercise
Sa02- However, they found that patients with noctur¬
nal desaturation also had evidence of deterioration in
gas exchange during exercise, with a rise in PaC02 and
lack of improvement in the physiologic dead-space
ventilation (Vd/Vt) ratio.
The mean Sa02 during sleep among patients in the
present report was only 3.5% less than awake levels,
although transient nonapneic desaturations to levels
less than 85% were seen in more than half the study
50% of patients with daytime
population, including
Pa02 greater than 60 mm Hg. The relatively modest
level of mean O2 desaturation among the overall group
likely reflects the fact that our study population had a
wide range of awake Pa02 levels, varying from 52 to 91
mm Hg, although all patients had severe airflow
obstruction, with a mean FEVi of 32.4 (9.1)% pre¬
dicted (Table 1). This study population was purposely
chosen according to pulmonary function test criteria of
severity rather than an arbitrary Pa02 level since we
wished to include a spectrum of COPD patients,
ranging from the two extremes of those with severe
airflow obstruction but relatively well-preserved blood
gas values to those with severe hypercapnic respiratory
failure and cor pulmonale. The terms pink-puffer and
blue-bloater are used in the context of the present
study simply as shorthand to indicate these two
extremes. We wished to examine the possibility that
patients at these two ends of the COPD spectrum
might show different patterns of desaturation during
While the present data provide
sleep andforexercise.
the
view
that pink puffer type COPD pa¬
support
tients are likely to desaturate more during exercise than
during sleep, the numbers are too small to draw any
definitive conclusions in this regard. Furthermore,
while the blue bloater patients with hypoxemia, hy¬
percapnia, and cor pulmonale had the most severe and
prolonged
degree of nocturnal desaturation, these pa¬
tients also had the most severe desaturation during
tween
exercise.
Oxygen
probably
desaturation during sleep in COPD is
caused by several mechanisms, one of
hypoventilation,thereparticularly
during ofREM
is
in¬
also
evidence
sleep.1213,31 However,
creased V/Q mismatching1,14 during sleep in COPD,
which contributes to gas exchange abnormalities. The
extent of the fall in Sa02 during sleep in individual
patients will also depend on the starting (presleep)
position on the oxyhemoglobin curve. It is difficult to
resolve the relative
ofthese various factors
which is
importance
Clinical
Investigations
without invasive measurements of gas exchange during
variable nature of respiration during REM
sleep. The
with possible variations in the respiratory quo¬
sleep,
tient during
and the larger body
stores of CO2 also make calculations based on the
alveolar air equation difficult to interpret. Despite
these difficulties, we hoped that the present study
would provide some useful data on this subject, as we
obtained an indirect measurement of PaC02 by con¬
tinuous monitoring of PtcC02, unlike previous studies
that relied on intermittent blood gas sampling.1'213,14
The continuous monitoring of PtcC02 helped us to
estimate Pa02 during sleep from the Sa02 trace, since
we could make an allowance for the effect of a chang¬
ing PaC02 on the oxyhemoglobin dissociation curve.
These measurements represent an estimate only, as
there are delays between the equilibration of PtcC02
and PaC02, as discussed above. Using this indirect
method, we found a somewhat larger fall in Pa02 and
rise in PtcC02 during sleep than some other studies of
COPD patients in whom arterial blood gases were
sampled intermittently,1314 but our findings are simi¬
lar to those of Koo et al.1 The maximum rise in PaC02
was 45% of the fall in Pa02 (Table 2), which is similar
to other reports.114
The continuous monitoring of PtcC02 showed that,
nature, the falls in Sa02 were
despite their transient
in
a
rise
PtcC02 a few minutes later,
accompanied by
the delay reflecting the time lag between change in
PaC02 and subsequent change in PtcC02.28 The
greater body storage capacity for CO2 did not seem to
prevent these transient rises in PtcC02. REM sleep, in
particular, was frequently characterized by irregular,
low tidal volume respiration on the record (Respitrace), and a high PtcC02 (Table 3). These observa¬
tions support hypoventilation as one of the major
causes of nocturnal desaturation in COPD, particularly
the similar rise in
during REM sleep. inHowever,
PtcC02 during sleep the major and minor desatu¬
rators suggests that both groups had a similar degree
of hypoventilation, and that factors such as lower po¬
sition on the oxyhemoglobin dissociation curve and/or
greater degrees of V/Q mismatching were responsible
for the greater degree of desaturation among major
desaturators.
As in other studies,317"19 we found that daytime
Pa02 correlates well with mean nocturnal Sa02, which
initially suggests that nocturnalofdesaturation may be
related to the presleep position hypoxemic patients
on the steeper portion of the oxyhemoglobin curve.
However, the patients who were major nocturnal de¬
saturators had a threefold greater fall in estimated
sleep Pa02 than the minor desaturators. We recognize
that the estimated Pa02 is not a precise measurement,
but the magnitude of difference in estimated Pa02
between major and minor desaturators strongly sup¬
hypoventilation,3'13
ports a real difference in this variable. This finding
suggests that the presleep position on the oxyhemo¬
globin dissociation curve was not the major determi¬
nant of the extent of O2 desaturation during sleep in
these subjects, since if this were the case, the fall in
calculated Pa02 should have been the same irrespec¬
tive of the Sa02. The much larger fall in estimated
Pa02 among the major desaturators, in conjunction
with the similar rise in PtcC02 in both patient groups,
supports the presence of gas exchange abnormalities
such as V/Q disturbances as a major cause ofthe excess
oxygen desaturation during sleep in major desatura¬
tors.
Numerous studies have found that patients with
awake hypercapnia are more likely to have nocturnal
oxygen desaturation,2"519 and we also found that all of
our hypercapnic patients had major nocturnal desatu¬
ration, despite similar pulmonary function to the normocapnics. However, we found that awake PaC02 is
not an independent predictor of nocturnal desatura¬
tion, which contrasts with the findings of some other
reports.17,19 A possible explanation for this discrepancy
is that, unlike these studies,17,19 we performed full
and respiratory monitoring on all
polysomnography
our patients, and were thus able to exclude apneic
events among all our patients, and to be confident of
sleep status. MacKeon et al18 also found that daytime
PaC02 was not an independent predictor of sleep
Sa02- There was a significant relationship between
PaC02 and the rise in sleep PtcC02 on sim¬
daytime
linear
regression analysis, but, as can be seen in
ple
the
Figure 2, relationship was weak, with a wide scat¬
ter of the data. We found that there was no significant
correlation on multiple regression analysis between
variables and the rise in sleep PtcC02 and we
daytime
also found a similar rise in PtcC02 during sleep among
both normocapnic and hypercapnic patients. These
findings suggest that there inis a similar degree of
hypoventilation during sleep all patients, regardless
of PaC02, secondary to the withdrawal of the wakefulness drive to breathe,33 and that the greater fall in
Sa02 during sleep among hypercapnic patients may be
due to worsening gas exchange abnormalities in addi¬
tion to their more marked baseline hypoxemia.
All except two of our patients desaturated during
exercise, and 14 of the total 19 patients had a fall in
exercise Sa02 greater than 5%. This represents a more
incidence of oxygen desaturation during ex¬
frequent
ercise in patients with COPD than reported in other
studies,8' and may be due to either a different patient
or to the fact that we use a treadmill rather
population
than cycle ergometer.35 Early studies of exercise
in COPD proposed the theory that
pathophysiology
with
normocapnic respiratory failure had
patients
greater impairment of exercise ability and were more
likely to desaturate during exercise than patients with
CHEST /109 / 2 / FEBRUARY, 1996
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393
failure.20 It was thought that
hypercapnic respiratory
who
patients tend to have a predominance
pink-puffer
of emphysema were already hyperventilating at rest,
and that they would be unable to increase their venti¬
lation further during exercise, while the blue bloater
types of patients had a greater capacity to increase
ventilation during exercise and were less incapacitated
data support the view
by dyspnea. While the present
that pink puffer patients are more likely to desaturate
during exercise than sleep, they do not support the
view that blue bloater patients will do the converse,
since the hypercapnic patients had twice as great a fall
but had
as the
in exercise
Sa02
normocapnic patients,
similar Ve max, V02 max, and exercise duration. Other
more recent studies have also found that patients with
oxygen desaturation during exercise are more likely to
be hypercapnic, with a further rise in PaC02 during
exercise, and to have evidence of an inability to
adequately decrease their dead-space during exer¬
cise. '15,16 As in other studies,34 there was poor corre¬
lation between exercise desaturation and pulmonary
function test results.
In conclusion, our findings indicate that COPD pa¬
tients desaturate significantly more during sleep than
exercise, and that hypoventilation and V/Q mismatch¬
ing represent the principal determinants of desatura¬
tion
during sleep.
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Clinical Investigations