Disordered Breathing and Oxygen Desaturation During Sleep in Patients with Chronic Obstructive Lung Disease (COLD)
JAMES W. WYNNE, M.D. A. JAY BLOCK, M.D. JUDITH HEMENWAY, M.D. LYNN A. HUNT, C.R.T.T. MICHAEL R. FLICK, M.D. Gainesville, Florida
From the Departments of Medicine (Pulmonary Division), Anesthesiology and Nursing, University of Florida College of Medicine: and the Veterans Administration Hospital, Gainesville, Florida. This study was supported in part by the Medical Research Service of the Veterans Administration, and by the Public Health Service Pulmonary Academic Award K07 H10012.2 from the National Heart, Lung, and Blood Institute. It was presented in part at the 26th Aspen Lung Conference, Aspen, Colorado, June 1978. Requests for reprints should be addressed to Dr. James W. Wynne, Department of Medicine (Pulmonary Division), Box J-225, University of Florida College of Medicine, Gainesville, Florida 32610. Manuscript accepted November 17. 1976.
Seven patients with chronic obstructive lung disease (COLD)were monitored during their overnight sleep to determine the occurrence of disordered breathing and oxygen desaturation. Nasal and oral airflows were sensed by thermistor probes, chest wall movement by impedance pneumography and kterial oxygen saturation by ear oximetry. These variables were correlated with electroencephalographic and electrooculographic tracings. The subjects had a mean base line oxygen saturation of 89.2 per cent and slept an average of 218 minutes. Six of these seven subjects had one to 30 episodes of oxygen desaturation (decrease more than 4 per centj, 4 seconds to 38 minutes in duration, with declines in saturation as great as 38 per cent. In two subjects, saturation dropped to less than 30 per cent. Breathing was disordered in five of the seven subjects and included apnea and hypopnea. Subjects experienced from nine to 37 episodes of disordered breathing. Disordered breathing caused 42 per cent of the episodes of desaturation, all of which were less than 1 minute in duration. The mean maximum declinein saturation was 7.8 per cent. All episodes of desaturation lasting longer than 5 minutes occurred in rapid eye movement (REM)sleep and were not caused by disorderedbreathing.Themeanmaximaldecrease in saturation was 22 per cent. This study reveals that disordered breathing is common in subjects with COLD and often causes desaturation but that it cannot explain all episodes of sleep desaturation. Continuous nocturnal monitoring of arterial oxygen saturation has revealed that sleeping patients with chronic obstructive lung disease [COLD] experience slight base line reductions in oxygen saturation. In addition, frequent severe desaturation occurs in an episodic fashion. These episodes have been demonstrated to last from seconds to hours and to number into the hundreds in a single night [l]. The mechanism is not known; however, in many cases the pattern is reminiscent of that seen in patients with the sleep apnea syndrome who experience episodic nocturna1 desaturation caused by repeated sleep-induced respiratory pauses. Less severe and less frequent alterations of respiration are known to occur during sleep in normal persons [&-5] and, in addition to apnea, may include rhythmic breathing and episodic hypopnea. We have demonstrated a relationship between changes in the breathing pattern and oxygen desaturation in patients with COLD monitored during short daytime naps [6]. However, the patients slept for only short periods, and sleep was not ‘documented by electroencephalographic monitoring. In the present study, we investigated the relationship between sleep-associated changes in the pattern of
April 1676
The American Journal of Medicine
Volume 66
573
DISORDERED BREATHING AND OXYGEN DESATURATION
TABLE I
Us)
Wsl@t FEV, (lb) Ws)
FRC Arterial Blood Db4a FEV,/FVC Gasss(mmHg) (% (% prSdlOtSd) prsdlctsd) pH Psf& PaCDs (%)
2 3 4
36 67 58 56
68 71 71 64
156 142 165 144
0.55 0.63 0.44
49 25 41 37
5 6
63 53
69 66
219 223
0.66 0.66
37 48
-
7
60
72
122
0.60
35
1
ET AL.
Characteristics of Patients with COLD
Cass Age Hsl$tt
No. (yr)
DURING SLEEP-WYNNE
1.26
25
Asssclalsd 9Mtmsls
135 195 159 124
7.38 7.41 7.39 7.43
54 66 64 64
45 35 38 43
96
172 188
7.42 7.41
62 68
43 39
None Peptic ulcer disease, alcohol abuse None Diabetes, hyperlipidemia, coronary artery disease Alcohol abuse Diabetes, peptic ulcer disease, colonlc polyps
23
196
7.40
56
41
Angina pectoris, intermittent claudlcation
48
53 46
NOTE:FE’.‘1= forced expiratory volume in 1 second, FEVt/FVC = the fraction of forced vital capacity measured by FEV,, DLcoss = steady state diffusing capacity, FRC = functional residual capacity, Pa02 = arterial oxygen tension, PaCOs = arterial carbon dioxide tension.
breathing and oxygen desaturation
in patients with
COLD during prolonged nocturnal sleep documented
by appropriate electrocardiographic graphic monitoring.
and electrooculo-
PATIENTS AND MEXHODS Seven subjects,all white men from 36 to 67 years of age (mean 56.1 years), were selected from the wards and clinics of the Gainesville Veterans Administration Hospital (Table I). All subjects were chosen on the basis of clinical history and physical examination indicative of COLD, abnormal results from pulmonary function tests, and by their willingness to be monitored during sleep. All were in a stable clinical state, and associated diseases were under maximum control. All denied excessive daytime somnolence. None of the patients was receiving sedative or psychotropic drugs at the time of the study. The subjects were monitored during sleep using standard polygraphic technics. Chest wall movement was sensed by impedance pneumography; nasal and oraI airflow was sensed by thermistor probes (Grass Instruments] in the nose and mouth; and oxygen saturation was measured by ear oximetry (Hewlett Packard No. 47201 A]. All these variables were recorded simultaneously on a multichannel recorder (Physiograph, Narco Biosystems). The electrocardiographic and
electrooculographic tracings were obtained simultaneously but recorded separately. Sleep was staged in 1 minute epochs according to the methods of Agnew and Webb [7]. Patients were also closely observed throughout the entire study for the presence of snoring, abnormal body movements and changes in position. Definitions: Oxygen desaturation was defined as a reduction of oxygen saturation more than 4 per cent from base fine sleeping levels. Disordered breathing was judged to be present if apnea or hypopnea was present. Apnea was defined as cessation of airflow at the nose and mouth lasting 10 seconds, and hypopnea was defined as a distinct episode of reduced airflow at the nose and mouth causing thermistor recording deflection of less than one-third base line levels for at least 10 seconds. Sleep period time was defined as the time from when the patient first fell asleep to the time when he last awakened; total
574
April 1979
The American
Journal of Medicine
Volume
sleep time was sleep period time less any time that the patient spent awake during the night after the initial onset of sleep.
RESULTS The pulmonary function test results of these patients indicated moderate to severe obstructive ventilatory disease (Table I). The mean forced expiratory volume in 1 second (FEV1) was 0.71 liters and the mean FEVl forced vital capacity (FVC) was 38.1 per cent. Determination of blood gas tensions in all subjects revealed mild to moderate hypoxemia without hypercarbia. The mean arterial oxygen tension (PaOa) was 63.5 mm Hg. Base line saturation determined by oximetry after 5 minutes of sleep varied from 72 to 94 per cent with a mean of 89.2 per cent. In general, the subjects slept poorly [Figure 1). The mean total sleep time was only 218 minutes, and almost 30 per cent of sleep period time was stage 0 sleep consistent with many awakenings during the night. However, all patients spent some time in stages I, II, III, IV and I-REM sleep. Stages I, II and I-REM sleep occupied the greatest percentages of sleep period time. Six of seven subjects had one or more episodes of oxygen desaturation; two patients (Cases 4 and 6) accounted for 68 per cent of all episodes of desaturation (Table II). The mean number of desaturation episodes per subject was 11.9, and the mean decrease in saturation per episode was 7.2 per cent. The greatest reduction in oxygen saturation was 36 per cent; two patients experienced saturations less than 50 per cent. The mean of the individual maximum decreases in oxygen saturation was 17 per cent. The mean percentage of total sleep time spent in sleep desaturation was 10.8, and two patients spent more than 25 per cent of total sleep time in sleep desaturation. Five of the seven subjects experienced some type of disordered breathing, including apnea or hypopnea (Table II]. The total number of episodes of disordered breathing per subject ranged from five to 74. Fortyseven of the 160 recorded episodes of disordered breathing were classified as apnea, the longest of which
66
DISORDERED
BREATHING
AND
OXYGEN DESATURATION
DURING SLEEP-WYNNE
ET AL.
80
PATIENTS SPT-2660136)min Ages 36-67
CONTROLS SPT-407(+46)min. Ages 50-59
Stage 0
Stage1
Stage II
P~.OOl
PC.05
P
-ao&
+00%
92%
/
93Ye 5on
71%
50%
Figure 3. Periodic breathing in patient with COLD during stage I sleep. Note both hypopnea and apnea causing oxygen desaturation. This figure is reproduced with permission from [9].
oxygen-hemoglobin dissociation curve, will cause much larger reductions in oxygen saturation. Therefore, abnormalities of oxygenation during sleep in patients with COLD are more likely to be noted in those studies employing continuous monitoring of oxygen saturation and composed of a large proportion of patients with low PaOz values. We have used continuous monitoring of oxygen saturation during sleep to study 27 patients with COLD, including those in the present study, and have documented episodes of desaturation in 22 of them [1,6]. All of these patients would be classified as having moderate to severe obstructive lung disease (mean FEV1, 1.02 liters). Their mean base line oxygen saturation was 87.5 per cent, a value that would be located just at the shoulder of the standard oxygen-hemoglobin dissociation curve. This may account for the high frequency of desaturation in our patients. Disordered breathing was also common among our patients, and in individual patients the number of such episodes was quite large. Several factors may account for this. First, we employed a broad definition of disordered breathing. We included not only episodes of apnea characterized by complete cessation of airflow but also episodes of hypopnea characterized by marked reductions in airflow. We did this because the sensitivity
of our monitoring equipment did not always allow accurate distinction between apnea and hypopnea, and because on many occasions desaturation occurred when there was hypopnea but not complete apnea. Secondly, we used an arbitrary definition of hypopnea which may have overestimated the frequency of disordered breathing. Finally, underlying all these problems is the fact that thermistor recordings do not provide true quantitative measurement of airflow. Nevertheless, we feel confident of our findings since generally all episodes of hypopnea were quite obvious, either because of their severity or because of associated events such as desaturation or a rhythmic breathing pattern. The age of our patients may have been another factor accounting for the high frequency of breathing abnormalities. Webb [4] has shown an increased incidence of periodic breathing in men aver 45 years of age. Furthermore, breathing abnormalities such as periodic breathing are known to occur more often during the period of drowsiness preceding true sleep and in the early stages of light sleep [Z].Whether it was because of their disease or the conditions under which our subjects were studied, their sleep patterns showed substantial differences from normal sleep patterns. Our patients awakened frequently and spent significantly more time in stage 0 and stage I sleep than would comparable
April 1979
The American Journal of Medicine
Volume 66
577
DISORDERED BREATHING AND OXYGEN DESATLJRATION DURING SLEEP-WYNNE
normal subjects. Therefore, they may have been more prone to the development of disordered breathing because of the predominance of light sleep. It is also possible that sleeping may blunt the normal reflex response of the respiratory control system to increased airway resistance [14]. In patients with COLD, many of whom already have decreased chemical sensitivity, this could lead to prolonged episodes of apnea and hypopnea. Finally, a consensus does not exist regarding the prevalence of disordered breathing in the general population in part due to differences in definitions, study technics and patient populations. In our own study of normal men [x?], performed under conditions similar to those in this study, 14 of 27 subjects had disordered breathing. In this group of normal subjects the mean age was 35 years, and only those hypopneic episodes that caused desaturation were noted. These results, as well as those obtained by Biilow [2] and Webb [4], suggest that the disordered breathing noted in our patients with COLD may be no more than a variation of a normal phenomenon. The mechanisms of sleep desaturation in COLD are not clear. Previous studies in which interval blood gas analyses were used to investigate this question have generally failed to appreciate the episodic nature of desaturation. Disordered breathing is certainly an important one. Forty-two per cent of the episodes of oxygen desaturation in our patients were caused either by apnea or hypopnea. These episodes, however, were generally short and only mild to moderately severe. Although single episodes of desaturation caused by disordered breathing occurred during all sleep stages, this form of desaturation was most likely to occur with the onset of sleep and during light sleep. A substantial number of episodes of desaturation, however, could not be attributed to disordered breathing and generally fell into two major categories: (1) There were short, minor alterations in saturation which in many cases appeared to be no more than base line fluctuations. The mechanisms underlying these changes were not obvious. They did not typically occur in any specific sleep stage and did not correlate with changes in body position, body movement or snoring (2). There were prolonged episodes of severe desaturation lasting longer than 5 minutes with declines in oxygen saturation as great as 36 per cent. These episodes occurred exclusively in REM sleep. Although periodic breathing and apnea occurred sporadically during these episodes, they could not in any way account for the extent of the desaturation noted. In general, nasal and oral airflow remained remarkably constant and unchanged from base
ET AL,
line values during these episodes. Since we did not measure intrapleural pressure, a continuous partial obstruction cannot be ruled out. We can only guess at the mechanisms for these changes. Arterial blood was not drawn and we cannot state whether the mechanism of hypoxemia was alveolar hypoventilation or inequality of ventilation and perfusion. However, blood gas analyses performed by Flick and Block [l] during similar episodes of desaturation in patients with COLD showed a predominance of ventilation-perfusion inequality. The only major clue to the mechanism of these episodes of prolonged desaturation is that they occurred only in REM sleep. A wide variety of physiologic changes are known to occur during this stage and might contribute to oxygen desaturation. One change that may be particularly pertinent to this problem is the dissociation of diaphragmatic and intercostal activity documented during REM sleep in cats [16] and in human subjects [17].Studies in human subjects have shown that the percentage of the tidal volume contributed by rib cage motion falls from 44 to 19 per cent when this occurs and that paradoxic motion of the rib cage often accompanies these changes. These events may be particularly relevant in patients with COLD who have shorter, flatter and less efficient diaphragms, and who rely to a greater extent on the activity of their intercostal muscles. Loss of intercostal muscle activity in these patients could lead either to alveolar hypoventilation or to changes in chest wall compliance with subsequent alterations in the ventilation-perfusion relationships in the lung. Finally, we made no systematic attempt in this study to assess the clinical significance of the changes we noted. Previous studies of patients with COLD have demonstrated serious arrhythmias during sleep which could be eliminated to some extent by the administration of oxygen [l]. Furthermore, studies of patients with the sleep apnea syndrome have also revealed arrhythmias as well as pulmonary and systemic hypertension directly associated with episodes of nocturnal desaturation [18]. We have similarly observed increased pulmonary vascular resistance associated with sleep desaturation in people with COLD. These episodes might serve as the precursors of pulmonary hypertension
D91.
All of these studies suggest that physiologic changes occurring during sleep have an important bearing on the pathophysiology of COLD and possibly other diseases as well. The clinical recognition and treatment of sleep-induced abnormalities may become an important aspect of the care of patients with COLD.
REFERENCES 1. Flick MR, Block AJ: Continuous in vivo monitoring of arterial oxygenation in chronic obstructive lung disease. Ann Intern Med 86: 725.1977. 2. Bulow K: Respiration and wakefulness in man. Acta Physiol Stand 59 (suppl209): 1.1963.
578
April 1979
The American Journal of Medicine
3.
4.
Volume 88
Robin ED, Whaley RD. Crump CH, et al.: Alveolar gas tensions, pulmonary ventilation and blood pH during physiologic sleep in normal subjects. J Clin Invest 37: 981, 1958. Webb P: Periodic breathing during sleep. J Appl Physio137:
DISORDERED BREATHING AND OXYGEN DESATURATION DURING SLEEP-WYNNE
899.1974. 5. Aserinsky E: Periodic respiratory pattern occurring in conJunction with eye movements during sleep. Science 156 763.1965. 6. Wynne JW. Block AJ, Hunt LA, et al.: Disordered breathing and oxygen desaturation during daytime naps. Johns Hopkins Med J 143: 3,1978. 7. Agnew HW Jr, Webb WB: Sleep stage scoring. Journal Supplement: Abstract Service of the American Psychological Association,‘Manuscript 293,1972. 8. Williams RL, Karacan I, Hursch CJ: EEG of Human Sleep: Clinical Applications. New York, John Wiley&Sons, New York, 1974. 9. Wynne JW. Block AJ. Hemenway J, et al.: Disordered breathing and oxygen desatumtion during sleep in patients with chronic obstructive pulmonary disease. Chest 735: 301s. 1978. 10. Koo W, Sax DA, Snider GL: Arterial blood gases and pH durinn sleen in chronic obstructive nuhnonarv disease. Am J Medv 58: 663,1975. 11. Pierce AK larrett CE. Werklk G lr. et al.: Resuiratorv function during sleep in patients with chronic obstructive lung disease. J Clin Invest 45: 631, IQ66 12. Trask CH, Cree EM: Oximeter studies on patients with
13.
14. 15. 16.
17. 18. 29.
April 1879
ET AL,
chronic obstructive emphysema, awake and during sleep. N Engl J Med 266: 63Q,lQ62. Leitch AG, Clancy LJ, Leggett RJE, et al.: Arterial blood gas tensions, hydrogen ion and electroencephalogram during sleep in patients with chronic ventilatory failure. Thorax 31: 730.1976. Isaza GD, Posner JD, Altose MD, et al.: Airway occlusion measures in awake and anesthetized goats. Resnir . Phvsiol . 27: 87,1976. Block AJ, Hunt L Wynne JW: Sleep desaturation. apnea and hwoventilation in normal subiects. Am Rev Respir Dis 117 (s-uppl): 95. 1978. Parmeggiani PL, Sabittini L: Electromyographic aspects of postural, respiratory, and thermoregulatory mechanisms in sleeping cats. Electroencephalogr Clin Neurophysiol 33: 1.1972. Tusiewicz K, Moldofsky H, Bryan AC, et al.: Mechanics of the rib cage and diaphragm during sleep. J Appl Physiol 43: 600.1977. Tilkian AG, Gulleminault C, Schroeder JS, et al.: Hemodynamics in sleet induced awea. Ann Intern Med 85: 714. 1976. Boysen PG, Wynne JW, Block A]: Oxygen saturation in “blue bloaters.” (Letter to the Editor). Lancet 1: 936,1978.
The American Journal of Medicine
Volume 86
879
JAMES W. WYNNE, M.D. A. JAY BLOCK, M.D. JUDITH HEMENWAY, M.D. LYNN A. HUNT, C.R.T.T. MICHAEL R. FLICK, M.D. Gainesville, Florida
From the Departments of Medicine (Pulmonary Division), Anesthesiology and Nursing, University of Florida College of Medicine: and the Veterans Administration Hospital, Gainesville, Florida. This study was supported in part by the Medical Research Service of the Veterans Administration, and by the Public Health Service Pulmonary Academic Award K07 H10012.2 from the National Heart, Lung, and Blood Institute. It was presented in part at the 26th Aspen Lung Conference, Aspen, Colorado, June 1978. Requests for reprints should be addressed to Dr. James W. Wynne, Department of Medicine (Pulmonary Division), Box J-225, University of Florida College of Medicine, Gainesville, Florida 32610. Manuscript accepted November 17. 1976.
Seven patients with chronic obstructive lung disease (COLD)were monitored during their overnight sleep to determine the occurrence of disordered breathing and oxygen desaturation. Nasal and oral airflows were sensed by thermistor probes, chest wall movement by impedance pneumography and kterial oxygen saturation by ear oximetry. These variables were correlated with electroencephalographic and electrooculographic tracings. The subjects had a mean base line oxygen saturation of 89.2 per cent and slept an average of 218 minutes. Six of these seven subjects had one to 30 episodes of oxygen desaturation (decrease more than 4 per centj, 4 seconds to 38 minutes in duration, with declines in saturation as great as 38 per cent. In two subjects, saturation dropped to less than 30 per cent. Breathing was disordered in five of the seven subjects and included apnea and hypopnea. Subjects experienced from nine to 37 episodes of disordered breathing. Disordered breathing caused 42 per cent of the episodes of desaturation, all of which were less than 1 minute in duration. The mean maximum declinein saturation was 7.8 per cent. All episodes of desaturation lasting longer than 5 minutes occurred in rapid eye movement (REM)sleep and were not caused by disorderedbreathing.Themeanmaximaldecrease in saturation was 22 per cent. This study reveals that disordered breathing is common in subjects with COLD and often causes desaturation but that it cannot explain all episodes of sleep desaturation. Continuous nocturnal monitoring of arterial oxygen saturation has revealed that sleeping patients with chronic obstructive lung disease [COLD] experience slight base line reductions in oxygen saturation. In addition, frequent severe desaturation occurs in an episodic fashion. These episodes have been demonstrated to last from seconds to hours and to number into the hundreds in a single night [l]. The mechanism is not known; however, in many cases the pattern is reminiscent of that seen in patients with the sleep apnea syndrome who experience episodic nocturna1 desaturation caused by repeated sleep-induced respiratory pauses. Less severe and less frequent alterations of respiration are known to occur during sleep in normal persons [&-5] and, in addition to apnea, may include rhythmic breathing and episodic hypopnea. We have demonstrated a relationship between changes in the breathing pattern and oxygen desaturation in patients with COLD monitored during short daytime naps [6]. However, the patients slept for only short periods, and sleep was not ‘documented by electroencephalographic monitoring. In the present study, we investigated the relationship between sleep-associated changes in the pattern of
April 1676
The American Journal of Medicine
Volume 66
573
DISORDERED BREATHING AND OXYGEN DESATURATION
TABLE I
Us)
Wsl@t FEV, (lb) Ws)
FRC Arterial Blood Db4a FEV,/FVC Gasss(mmHg) (% (% prSdlOtSd) prsdlctsd) pH Psf& PaCDs (%)
2 3 4
36 67 58 56
68 71 71 64
156 142 165 144
0.55 0.63 0.44
49 25 41 37
5 6
63 53
69 66
219 223
0.66 0.66
37 48
-
7
60
72
122
0.60
35
1
ET AL.
Characteristics of Patients with COLD
Cass Age Hsl$tt
No. (yr)
DURING SLEEP-WYNNE
1.26
25
Asssclalsd 9Mtmsls
135 195 159 124
7.38 7.41 7.39 7.43
54 66 64 64
45 35 38 43
96
172 188
7.42 7.41
62 68
43 39
None Peptic ulcer disease, alcohol abuse None Diabetes, hyperlipidemia, coronary artery disease Alcohol abuse Diabetes, peptic ulcer disease, colonlc polyps
23
196
7.40
56
41
Angina pectoris, intermittent claudlcation
48
53 46
NOTE:FE’.‘1= forced expiratory volume in 1 second, FEVt/FVC = the fraction of forced vital capacity measured by FEV,, DLcoss = steady state diffusing capacity, FRC = functional residual capacity, Pa02 = arterial oxygen tension, PaCOs = arterial carbon dioxide tension.
breathing and oxygen desaturation
in patients with
COLD during prolonged nocturnal sleep documented
by appropriate electrocardiographic graphic monitoring.
and electrooculo-
PATIENTS AND MEXHODS Seven subjects,all white men from 36 to 67 years of age (mean 56.1 years), were selected from the wards and clinics of the Gainesville Veterans Administration Hospital (Table I). All subjects were chosen on the basis of clinical history and physical examination indicative of COLD, abnormal results from pulmonary function tests, and by their willingness to be monitored during sleep. All were in a stable clinical state, and associated diseases were under maximum control. All denied excessive daytime somnolence. None of the patients was receiving sedative or psychotropic drugs at the time of the study. The subjects were monitored during sleep using standard polygraphic technics. Chest wall movement was sensed by impedance pneumography; nasal and oraI airflow was sensed by thermistor probes (Grass Instruments] in the nose and mouth; and oxygen saturation was measured by ear oximetry (Hewlett Packard No. 47201 A]. All these variables were recorded simultaneously on a multichannel recorder (Physiograph, Narco Biosystems). The electrocardiographic and
electrooculographic tracings were obtained simultaneously but recorded separately. Sleep was staged in 1 minute epochs according to the methods of Agnew and Webb [7]. Patients were also closely observed throughout the entire study for the presence of snoring, abnormal body movements and changes in position. Definitions: Oxygen desaturation was defined as a reduction of oxygen saturation more than 4 per cent from base fine sleeping levels. Disordered breathing was judged to be present if apnea or hypopnea was present. Apnea was defined as cessation of airflow at the nose and mouth lasting 10 seconds, and hypopnea was defined as a distinct episode of reduced airflow at the nose and mouth causing thermistor recording deflection of less than one-third base line levels for at least 10 seconds. Sleep period time was defined as the time from when the patient first fell asleep to the time when he last awakened; total
574
April 1979
The American
Journal of Medicine
Volume
sleep time was sleep period time less any time that the patient spent awake during the night after the initial onset of sleep.
RESULTS The pulmonary function test results of these patients indicated moderate to severe obstructive ventilatory disease (Table I). The mean forced expiratory volume in 1 second (FEV1) was 0.71 liters and the mean FEVl forced vital capacity (FVC) was 38.1 per cent. Determination of blood gas tensions in all subjects revealed mild to moderate hypoxemia without hypercarbia. The mean arterial oxygen tension (PaOa) was 63.5 mm Hg. Base line saturation determined by oximetry after 5 minutes of sleep varied from 72 to 94 per cent with a mean of 89.2 per cent. In general, the subjects slept poorly [Figure 1). The mean total sleep time was only 218 minutes, and almost 30 per cent of sleep period time was stage 0 sleep consistent with many awakenings during the night. However, all patients spent some time in stages I, II, III, IV and I-REM sleep. Stages I, II and I-REM sleep occupied the greatest percentages of sleep period time. Six of seven subjects had one or more episodes of oxygen desaturation; two patients (Cases 4 and 6) accounted for 68 per cent of all episodes of desaturation (Table II). The mean number of desaturation episodes per subject was 11.9, and the mean decrease in saturation per episode was 7.2 per cent. The greatest reduction in oxygen saturation was 36 per cent; two patients experienced saturations less than 50 per cent. The mean of the individual maximum decreases in oxygen saturation was 17 per cent. The mean percentage of total sleep time spent in sleep desaturation was 10.8, and two patients spent more than 25 per cent of total sleep time in sleep desaturation. Five of the seven subjects experienced some type of disordered breathing, including apnea or hypopnea (Table II]. The total number of episodes of disordered breathing per subject ranged from five to 74. Fortyseven of the 160 recorded episodes of disordered breathing were classified as apnea, the longest of which
66
DISORDERED
BREATHING
AND
OXYGEN DESATURATION
DURING SLEEP-WYNNE
ET AL.
80
PATIENTS SPT-2660136)min Ages 36-67
CONTROLS SPT-407(+46)min. Ages 50-59
Stage 0
Stage1
Stage II
P~.OOl
PC.05
P
-ao&
+00%
92%
/
93Ye 5on
71%
50%
Figure 3. Periodic breathing in patient with COLD during stage I sleep. Note both hypopnea and apnea causing oxygen desaturation. This figure is reproduced with permission from [9].
oxygen-hemoglobin dissociation curve, will cause much larger reductions in oxygen saturation. Therefore, abnormalities of oxygenation during sleep in patients with COLD are more likely to be noted in those studies employing continuous monitoring of oxygen saturation and composed of a large proportion of patients with low PaOz values. We have used continuous monitoring of oxygen saturation during sleep to study 27 patients with COLD, including those in the present study, and have documented episodes of desaturation in 22 of them [1,6]. All of these patients would be classified as having moderate to severe obstructive lung disease (mean FEV1, 1.02 liters). Their mean base line oxygen saturation was 87.5 per cent, a value that would be located just at the shoulder of the standard oxygen-hemoglobin dissociation curve. This may account for the high frequency of desaturation in our patients. Disordered breathing was also common among our patients, and in individual patients the number of such episodes was quite large. Several factors may account for this. First, we employed a broad definition of disordered breathing. We included not only episodes of apnea characterized by complete cessation of airflow but also episodes of hypopnea characterized by marked reductions in airflow. We did this because the sensitivity
of our monitoring equipment did not always allow accurate distinction between apnea and hypopnea, and because on many occasions desaturation occurred when there was hypopnea but not complete apnea. Secondly, we used an arbitrary definition of hypopnea which may have overestimated the frequency of disordered breathing. Finally, underlying all these problems is the fact that thermistor recordings do not provide true quantitative measurement of airflow. Nevertheless, we feel confident of our findings since generally all episodes of hypopnea were quite obvious, either because of their severity or because of associated events such as desaturation or a rhythmic breathing pattern. The age of our patients may have been another factor accounting for the high frequency of breathing abnormalities. Webb [4] has shown an increased incidence of periodic breathing in men aver 45 years of age. Furthermore, breathing abnormalities such as periodic breathing are known to occur more often during the period of drowsiness preceding true sleep and in the early stages of light sleep [Z].Whether it was because of their disease or the conditions under which our subjects were studied, their sleep patterns showed substantial differences from normal sleep patterns. Our patients awakened frequently and spent significantly more time in stage 0 and stage I sleep than would comparable
April 1979
The American Journal of Medicine
Volume 66
577
DISORDERED BREATHING AND OXYGEN DESATLJRATION DURING SLEEP-WYNNE
normal subjects. Therefore, they may have been more prone to the development of disordered breathing because of the predominance of light sleep. It is also possible that sleeping may blunt the normal reflex response of the respiratory control system to increased airway resistance [14]. In patients with COLD, many of whom already have decreased chemical sensitivity, this could lead to prolonged episodes of apnea and hypopnea. Finally, a consensus does not exist regarding the prevalence of disordered breathing in the general population in part due to differences in definitions, study technics and patient populations. In our own study of normal men [x?], performed under conditions similar to those in this study, 14 of 27 subjects had disordered breathing. In this group of normal subjects the mean age was 35 years, and only those hypopneic episodes that caused desaturation were noted. These results, as well as those obtained by Biilow [2] and Webb [4], suggest that the disordered breathing noted in our patients with COLD may be no more than a variation of a normal phenomenon. The mechanisms of sleep desaturation in COLD are not clear. Previous studies in which interval blood gas analyses were used to investigate this question have generally failed to appreciate the episodic nature of desaturation. Disordered breathing is certainly an important one. Forty-two per cent of the episodes of oxygen desaturation in our patients were caused either by apnea or hypopnea. These episodes, however, were generally short and only mild to moderately severe. Although single episodes of desaturation caused by disordered breathing occurred during all sleep stages, this form of desaturation was most likely to occur with the onset of sleep and during light sleep. A substantial number of episodes of desaturation, however, could not be attributed to disordered breathing and generally fell into two major categories: (1) There were short, minor alterations in saturation which in many cases appeared to be no more than base line fluctuations. The mechanisms underlying these changes were not obvious. They did not typically occur in any specific sleep stage and did not correlate with changes in body position, body movement or snoring (2). There were prolonged episodes of severe desaturation lasting longer than 5 minutes with declines in oxygen saturation as great as 36 per cent. These episodes occurred exclusively in REM sleep. Although periodic breathing and apnea occurred sporadically during these episodes, they could not in any way account for the extent of the desaturation noted. In general, nasal and oral airflow remained remarkably constant and unchanged from base
ET AL,
line values during these episodes. Since we did not measure intrapleural pressure, a continuous partial obstruction cannot be ruled out. We can only guess at the mechanisms for these changes. Arterial blood was not drawn and we cannot state whether the mechanism of hypoxemia was alveolar hypoventilation or inequality of ventilation and perfusion. However, blood gas analyses performed by Flick and Block [l] during similar episodes of desaturation in patients with COLD showed a predominance of ventilation-perfusion inequality. The only major clue to the mechanism of these episodes of prolonged desaturation is that they occurred only in REM sleep. A wide variety of physiologic changes are known to occur during this stage and might contribute to oxygen desaturation. One change that may be particularly pertinent to this problem is the dissociation of diaphragmatic and intercostal activity documented during REM sleep in cats [16] and in human subjects [17].Studies in human subjects have shown that the percentage of the tidal volume contributed by rib cage motion falls from 44 to 19 per cent when this occurs and that paradoxic motion of the rib cage often accompanies these changes. These events may be particularly relevant in patients with COLD who have shorter, flatter and less efficient diaphragms, and who rely to a greater extent on the activity of their intercostal muscles. Loss of intercostal muscle activity in these patients could lead either to alveolar hypoventilation or to changes in chest wall compliance with subsequent alterations in the ventilation-perfusion relationships in the lung. Finally, we made no systematic attempt in this study to assess the clinical significance of the changes we noted. Previous studies of patients with COLD have demonstrated serious arrhythmias during sleep which could be eliminated to some extent by the administration of oxygen [l]. Furthermore, studies of patients with the sleep apnea syndrome have also revealed arrhythmias as well as pulmonary and systemic hypertension directly associated with episodes of nocturnal desaturation [18]. We have similarly observed increased pulmonary vascular resistance associated with sleep desaturation in people with COLD. These episodes might serve as the precursors of pulmonary hypertension
D91.
All of these studies suggest that physiologic changes occurring during sleep have an important bearing on the pathophysiology of COLD and possibly other diseases as well. The clinical recognition and treatment of sleep-induced abnormalities may become an important aspect of the care of patients with COLD.
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Robin ED, Whaley RD. Crump CH, et al.: Alveolar gas tensions, pulmonary ventilation and blood pH during physiologic sleep in normal subjects. J Clin Invest 37: 981, 1958. Webb P: Periodic breathing during sleep. J Appl Physio137:
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899.1974. 5. Aserinsky E: Periodic respiratory pattern occurring in conJunction with eye movements during sleep. Science 156 763.1965. 6. Wynne JW. Block AJ, Hunt LA, et al.: Disordered breathing and oxygen desaturation during daytime naps. Johns Hopkins Med J 143: 3,1978. 7. Agnew HW Jr, Webb WB: Sleep stage scoring. Journal Supplement: Abstract Service of the American Psychological Association,‘Manuscript 293,1972. 8. Williams RL, Karacan I, Hursch CJ: EEG of Human Sleep: Clinical Applications. New York, John Wiley&Sons, New York, 1974. 9. Wynne JW. Block AJ. Hemenway J, et al.: Disordered breathing and oxygen desatumtion during sleep in patients with chronic obstructive pulmonary disease. Chest 735: 301s. 1978. 10. Koo W, Sax DA, Snider GL: Arterial blood gases and pH durinn sleen in chronic obstructive nuhnonarv disease. Am J Medv 58: 663,1975. 11. Pierce AK larrett CE. Werklk G lr. et al.: Resuiratorv function during sleep in patients with chronic obstructive lung disease. J Clin Invest 45: 631, IQ66 12. Trask CH, Cree EM: Oximeter studies on patients with
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chronic obstructive emphysema, awake and during sleep. N Engl J Med 266: 63Q,lQ62. Leitch AG, Clancy LJ, Leggett RJE, et al.: Arterial blood gas tensions, hydrogen ion and electroencephalogram during sleep in patients with chronic ventilatory failure. Thorax 31: 730.1976. Isaza GD, Posner JD, Altose MD, et al.: Airway occlusion measures in awake and anesthetized goats. Resnir . Phvsiol . 27: 87,1976. Block AJ, Hunt L Wynne JW: Sleep desaturation. apnea and hwoventilation in normal subiects. Am Rev Respir Dis 117 (s-uppl): 95. 1978. Parmeggiani PL, Sabittini L: Electromyographic aspects of postural, respiratory, and thermoregulatory mechanisms in sleeping cats. Electroencephalogr Clin Neurophysiol 33: 1.1972. Tusiewicz K, Moldofsky H, Bryan AC, et al.: Mechanics of the rib cage and diaphragm during sleep. J Appl Physiol 43: 600.1977. Tilkian AG, Gulleminault C, Schroeder JS, et al.: Hemodynamics in sleet induced awea. Ann Intern Med 85: 714. 1976. Boysen PG, Wynne JW, Block A]: Oxygen saturation in “blue bloaters.” (Letter to the Editor). Lancet 1: 936,1978.
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