Operation Everest II: Arterial Oxygen Saturation and Sleep at Extreme Simulated Altitude 1- 3
JAMES D. ANHOLM, A. C. PETER POWLES, RALPH DOWNEY III, CHARLES S. HOUSTON, JOHN R. SUTTON, MICHAEL H. BONNET, and ALLEN CYMERMAN With the technical assistance of Darlene Tyler
Introduction Sleep disturbances at high altitude frequently occur among climbers (1-4). Despite considerable interest in altitude physiology, only a few studies describing the extent of sleep disruption are available, and they are limited to altitudes below 4,400 m (4-8). Because climbers routinely describe worsening of sleep as altitude increases, it seems likely that there is an inverse relationship between sleeping altitude and sleep quality. There is no information available on sleep stages at the extreme altitudes (above 7,000 to 8,000 m) typically involved in Himalayan mountaineering. Periodic breathing during sleep at altitude has been known at least since the description of Mosso in 1898 (9). This breathing pattern is almost a universal finding at altitude. Lahiri and colleagues recently described periodic breathing during sleep in both Sherpas and sojourners up to 5,400 m, but these studies were limited by the difficulties imposed by the mountain environment, and no attempt was made to relate sleep stages to breathing pattern (5, 6). Periodic breathing has been thought to be a major cause of sleep-related arterial oxygen desaturation (10, 11), although others have suggested that periodic breathing during sleep in climbers may actually improve saturations during sleep (12). West and coworkers also studied periodic breathing during sleep in climbers at 6,300 m and 8,050 m on Mt. Everest, but measured arterial oxygen saturation only up to 6,300 m (13). Anecdotal reports have indicated disturbed sleep at very high altitudes, but data to support this are lacking. Poor sleep quality at sea level may adversely affect daytime mental performance and motor function (14, 15). Additionally, Hornbein and colleagues have recently drawn attention to central nervous system abnormalities in climbers or subjects
SUMMARY Frequent sleep disturbances and desaturatlon during sleep are common at high altitude, but few data are available from the highest altitudes at which humans are known to sleep. Because sleep fragmentation at low altitude may Impair mental function and oxygen deprivation produces lasting central nervous system abnormalities, a better understanding of the sevarlty of sleep disturbances and oxygen desaturatlon at extreme altitudes Is Important. The purpose of this study was to determine the severity of sleep disturbance and the extent of arterial oxygen desaturatlon at extreme simulated altitude. Out of eight healthy male subject volunteers who started, five aged 27.2 ± 1.5 yr completed the stUdy during 6 weeks of progresslva hypobaric hypoxia In a decompression chamber. The men were studied at barometric pressures of 760, 429, 347, 282 mm Hg and following return to 760 mm Hg. All demonstrated frequent nighttime awakenings (37.2 awakenings per subject per night at 282 mm Hg, decreasing significantly to 14.8 on return to sea level, p < 0.05). Total sleep time decreased from 337 ± 30 min at 760 mm Hg to 167 ± 44 min at 282 mm Hg (p < 0.01). Rapid eye movement (REM) sleep decreased from 17.9% ± 6.0% of sleep time at sea level to 4.0% ± 3.3% at 282 mm Hg (p < 0.01). Sleep continuity as reflected by brief arousals Increased from 22 ± 6 arousals per hour of sleep at sea level to 161 ± 66 arousals per hour at 282 mm Hg (p < 0.01). All subJects showed arterial oxygen desaturatlon proportional to the altitude. The average oxygen saturation (Sa0 2 ) was 79% ± 3% at 429 mm Hg, 66% ± 6% at 347 mm Hg, and 52% ± 2% at 282 mm Hg. Sleep stage had only a minimal effect on Sa0 2 at any altitude. Sa0 2 was negatively correlated with brief sleep arousals, r = -0.72, P < 0.01. All subJects demonstrated periodic breathing with apneas throughout much of the night at 347 and 282 mm Hg. These data Indicate that sleep quality progressively worsens as Sa0 2 decreases despite lack of progressive changes In sleep stages at altitude. This study extends previous Information on the sevarlty of desaturation during sleep, and suggests that Improvements In oxygenation might prove beneficial In restoring consolidated sleep, possibly even Improving daytime performance. AM REV RESPIR DIS 1992; 145:817-828
with prolonged hypoxic exposure (16). Because oxygen saturation during sleep at altitude may be lower than daytime values and because severe oxygen desaturation may be an important determinant of sleep quality, we sought to determine the extent of sleep impairment and oxygen desaturation at extreme simulated altitude. The primary purpose of this study was to determine whether progressive changes in sleep quality occurred assimulated altitude increased and whether these sleep changes were related to arterial oxygen saturation (Sao.). Methods Subjects Eight healthy male subjects aged 26.8 ± 3.0 yr were studied during a 40-day exposure to increasing hypobaric hypoxia. Eight healthy volunteers were invited from among 30 applicants to serve as subjects; selection was
based on motivation, personality, interest in physiology, fitness, and sports. The subjects' characteristics and other aspects of this study have been described in detail elsewhere (17). Each participant signed an informed consent
(Receivedin originalform December 14, 1990and in revised form June 10, 1991) 1 From the Department of Medicine, Lorna Linda University, Lorna Linda, California, the Department of Medicine, Cardiorespiratory Unit, McMaster University Medical Center, Hamilton, Ontario, Canada, and the Altitude Research Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. 2 Supported in part by U.S. Army Research and Development Command Contract DAMDI7-85-C5206, and by the Arctic Institute of North America. 3 Correspondence and requests for reprints should be addressed to James D. Anholm, M.D., Jerry L. Pettis Memorial Veterans' Hospital, Pulmonary Section (11IP), 11201 Benton Street, Lorna Linda, CA 92357.
817
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Days in Chamber Fig. 1. The ascent profile of the study showing the times spent at each altitude. Nights during which sleep studies were performed are indicated by solid squares (.). During the later part of ascent, on multiple occasions sleeping altitude was lower than the daytime altitude. When this occurred, sleeping altitude is indicated by open circles (0). During the last 7 days at altitude, one or more subjects were taken to the "summif' at the quivalent of 8,848 m for daytime studies, as indicated by arrows pointing upward. During this period, subjects not undergoing sleep studies slept at ICAO altitudes of 7,000 to 7,300 m, whereas subjects having sleep studies performed slept at 282 mm Hg (7,620 m).
at the beginning of the study, and the studies were approved by the human subjects committees of the various participating institutions. Only two subjects had had extensive altitude climbing experience, one to 7,000 m and the other to 6,000 m. None had been above 2,000 m in the 6 months prior to the study. The studies were performed in the decompression chamber ofthe U.S. Army Research Institute of Environmental Medicine, Natick, MA. The subjects lived continuously in the chamber, which was gradually decompressed to simulate ascent to altitude. The ascent profile indicating the altitudes at which sleep studies were performed is shown in figure 1. All subjects reported good nocturnal sleep prior to this study. Five subjects completed all of the sleep studies. Subject 6 refused further sleep studies above 429 mm Hg. Subject 7 had to be removed from the chamber because of a brief hypoxic episode after reaching 380 mm Hg and thus was only studied at sea level and at 429 mm Hg. Subject 5 was removed from the chamber for a brief hypoxic reaction at 282 mm Hg prior to the sleep study at this altitude. Subjects 5 and 7 experienced transient loss ofconsciousness and/or slurred speech or impaired motor function. All impairment was temporary, and both men fully recovered on descent to sea level. The data reported here, unless otherwise indicated, include the five subjects who completed all studies.
Sleep Studies The decompression chamber consisted of a living area and a smaller study chamber connected by an airlock. Chamber temperature, relative humidity, and FI02 were monitored and kept between 18to 22° C, 50 to 80% and at 1'\J20.9OJo, respectively(17). Altitude equivalents were obtained from the Manual of the ICAO Standard Atmosphere (18).Sleep stud-
ies weredone at the followingbarometric pressures and equivalent ICAO [International Civil Aviation Organization] altitudes: 760 mm Hg (sea level), 429 mm Hg (4,572 m), 347 mm Hg (6,100m), 282 mm Hg (7,620 m), and again following descent to sea level. Above 282 mm Hg the relationship between barometric pressure and altitude differs increasingly from that predicted by the ICAO pressure-altitude curve (19,20). Thus, 282 mm Hg is approximately 8,000 m on Mt. Everest, but corresponds to an ICAO altitude of only 7,620 m. Standard sleep recordings weremade using electrodes for monitoring the central electroencephalogram (EEG) (C3-A2 and/or C 4 At) as well as electrodes attached above or below the outer canthus of each eye for detecting rapid eye movement (REM) sleep. All EEG data and respiratory data from an inductance system wererecorded on a polygraph (ModeI8-IOBC; Grass Instruments, Quincy, MA). In addition, arterial oxygen saturation (Sao 2) by ear oximeter (Model 47201A; Hewlett-Packard, Palo Alto, CAl and the electrocardiogram (ECG) wererecorded continuously throughout the night. Chest and abdominal respiratory excursions weremonitored using an inductance system (Respitrace'"; Ambulatory Monitoring, Ine., Ardsley, NY). This inductance system was used uncalibrated but adjusted to give good abdominal and rib-cage signals. Minute ventilation was measured by having subjects wear a soft, close-fitting face mask (Downs CPAP mask; Vital Signs, Totowa, NJ) with a pneumotachograph attached to the inspiratory port. This pneumotachograph was calibrated at the study altitude using a l-L syringe at various flow rates before and intermittently during each night's studies. The mask allowed the addition of oxygen, carbon dioxide, or nitrogen to the inspired air to perform the ventilatory response studies, which
will be reported separately. During the time at altitude, no alcoholic beverages, caffeine, or other drugs known to alter sleep were consumed by any of the subjects prior to their sleep study. Acetaminophen was used to treat altitude-related headaches. The subjects were studied in pairs for the entire night. While they slept, supplemental oxygen, nitrogen, or carbon dioxide was administered to them intermittently throughout the night to assess ventilatory responses to hypoxia and hypercapnia. These responses were of varying lengths; however, the total time occupied by the responses was usually less than 25% ofthe night. All data from the control of breathing studies wererecorded on separate strip chart recorders from the sleep polygraph. Sleep recordings were made at a paper speed of 15mm/s (20-sepochs) throughout the night. Sleep stages werescored according to Rechtschaffen and Kales (21)by an experienced sleep technician. Definitions and formulas used in calculating sleep variables are as follows: total sleep time (TST) is the total number of minutes of Stages 1,2, 3, 4, REM, and movement time. The percentage of time in any sleep stage is calculated from the number of minutes of that sleep stage divided by the sum of TST plus any time spent awake during the night after the first occurrence of Stage 1. Total time in bed (TIB) is the total time from the start to finish of recording, regardless of whether the subject was awake or asleep. Sleep efficiency (SE) equals TST divided by TIB. A nighttime awakening is defined as art awake EEG pattern for one half or more of the standard epoch (i.e, 10 s or more). An arousal is a brief (2 to 10s) EEG disturbance consisisting of the appearance of alpha activity, a stage change, and evoked K-complex, EEG speeding (a clearly noticeable increase in EEG frequency overthe previous frequency), or movement (14,15,22,23). These arousals are not scored as awakenings, and subjects typically do not remember most of the arousals on awakening in the morning. Above Sao, readings of 50%, the HewlettPackard oximeter readings correlate wellwith arterial blood samples, but below 50% Sao 2, the oximeter significantly underestimates saturation (24).We developed a specificcorrelation factor by matching the measured arterial blood Sao2 values to simultaneous oximeter values during the daytime Operation Everest II studies. Using this factor, true Sao, = (oximeter reading + 19)/1.2 over the entire range of Sao, values (25). This equation was developed from a subset of the data of Forte and colleagues (25). It givessimilar, but not identical, values to that of Forte's equation. This formula also givessomewhat different values than does the correction suggested by Douglas and coworkers (24) that below 50% San, the true Sao, = observed Sao, + 'i'2(50 - observed Sao2). The average arterial oxygen saturation in each sleep stage was determined by adding the average saturation during each minute in a particular stage and dividing by the time in minutes in that stage. The time occupied
SATURATION AND SLEEP AT ALTITUDE
by the ventilatory response tests and an additional 4 min after resumption of breathing room air following chemosensitivity testing was excluded from this analysis. Periodic breathing as used here refers to a repetitive cyclicrespiratory pattern with or without apnea. Apnea is the cessation of breathing for a period of 10 s or longer, characterized by the absence of respiratory movement on the respiratory tracing. Apneas may be of two types, central or obstructive. Central apnea refers to those apneas characterized by an absence of respiratory movement of the chest wall as well as the absence of air flow. Obstructive apnea refers to those apneas in which air flow is obstructed in the upper airway but respiratory efforts continue, as evidenced by chest-wall movement during the apnea. No obstructive apneas were observed in this study. The term respiratory pause refers to a cessation of the normal breathing pattern for less than 10 s. The sleep-stagedata wereanalyzed by analysis of variance for repeated measurements for changes in the percent time in each stage at each altitude (26). Post hoc analysis using Newman-Keulscomparisons weremade when appropriate. A p value of less than 0.05 was considered significant.
Results
Altitude Effects on Sleep All subjects complained to some degree of poor sleep throughout the Operation Everest II study. These complaints were primarily difficulty falling asleep, frequent nighttime awakenings, and feeling less refreshed in the morning than expected. Some of these complaints were unrelated to altitude but due to the monitoring equipment and conditions of the sleep studies. Sleep difficulties were present in some subjects even on nights when sleep recordings were not done. Sleep variables are presented in table 1. Because it was not possible to study all subjects on their first night at each altitude, table 1 also shows the number of days acclimatizing prior to the sleep study. At sea level prior to ascent, subjects were awake 9.5070 ± 7.8% of the night, compared with 1.3% of the night that has previously been reported in normal young adults. Similarly, slow-wave sleep was reduced from what would be normally expected for healthy young adults. Time awake increased from 9.5% ± 7.8% of the night at sea level 41.1% ± 15.7070, 25.2070 ± 10.1070, and 45.8070 ± 21.2% at 4,572 m, 6,100m, and 7,620 m, respectively (p < 0.05 sea level compared with 4,572 m, and 7,620 m). Likewise, REM sleep was reduced from 17.9070 ± 6.0070 of the night at sea levelto 5.4070 ± 1.6070, 9.2070 ± 2.2%, and 4.0% ± 3.3070 at 4,572 m, 6,100 m, and 7,620 m, respec-
819
tively (p < 0.05 sea level compared with 65.5 at 7,620 m (282 mm Hg). Brief 4,572 m, 6,100 m, and 7,620 m). On re- arousals were highly negatively correlatturn to sea level, REM sleep increased ed with arterial oxygen saturation, r = relative to nights at altitude, with REM - 0.72, p < 0.01. now occupying 20.1070 ± 5.9% of the Two further indices of sleep quality night in REM sleep. shown in table 2 are the Top 1 and Top Slow-wave sleep (Stages 3 + 4) oc- 5 intervals. These numbers refer to the cupied 6.8070 ± 3.6% of the night at sea longest and the fifth longest arousal-free level compared with the normal value of interval per 100arousals and serve as an approximately 21070 ± 5070 (27). Slow- indication of the distribution of arousalwave sleep remained the same during al- free sleep periods. The Top 5 intervals titude exposure (3.7070 ± 6.3070, p = NS), decreased from 11.9 ± 3.1 min at sea level then increased to 10.6070 ± 8.6% follow- to 5.1 ± 3.6 min at 4,572 m, 4.0 ± 3.1 ing return to sea level. min at 6,100 m, and 1.5 ± 0.9 min at Since hypoxic and hypercapnic ventila- 7,620 m. Other values for Top 1 are inditory response testing during the night cated in the table. Thus, a Top 1 value may have interfered with sleep, the of 7.2 min at 7,620 m indicates that the changes in sleep stages were reanalyzed longest period of undisrupted sleep was after excluding this time (f\J20% of TIB). only 7.2 min. This analysis indicated that chemosensiAltitude Effects on Breathing tivity testing disrupted sleep by signifiand Saturation cantly increasing nighttime awakenings at sea level and 6,100 m (347 mm Hg). At and above 4,572 m (429 mm Hg), all Additionally, this testing reduced Stage subjects showed periodic breathing with 3 sleep from 2.0070 ± 0.9% to 1.1 ± 0.6070 apneas during the night. All apneas and at 6,100 m (347 mm Hg), but also de- respiratory pauses at all altitudes studcreased movement time at 6,100 m. No ied were central, because when no airother significant differences were found. flow occurred at the mouth, there was The TIB during the night was the same no chest or abdominal movement. Periat all altitudes. The equipment worn by odic breathing with or without apneas the subjects and the hypoxic and hyper- occurred in all subjects prior to ventilacapnic ventilatory response testing was tory response testing. Apneas were elimsimilar at all altitudes. These ventilatory inated when supplementary oxygen was responses had very little overall effect on administered, but periodic breathing persleep stages. Thus, the altitude-related sisted (figure 2). Apneas reappeared soon changes in sleep stages and TST were not after return to ambient air (figure 3). Addue to alterations in time available for . dition of 2 to 4070 carbon dioxide to the sleep or monitoring equipment worn, but inspired gas mixture also eliminated aprather to the sleep disruption that the sub- neas, even though fluctuation in tidal voljects experienced. ume remained (figure 4). Periodic breathSleep continuity deteriorated at alti- ing produced an oscillation in Sa02 of tude, as evidenced by SE (TST/TIB) and 6.6 ± 1.9%. There was no significant the number of awakenings compared difference in the fluctuation of Sa02 at with sea level. SE was 88.6070 ± 8.2070 different altitudes. At the highest altiat sea level and 55.5070 ± 15.5070 at tudes studied, the subjects reported con4,572 m (429 mm Hg), p < 0.05. Sleep siderable difficulty sleeping, but would studies at 6,100 m and 7,620 m did not promptly fall asleep when low-flow oxyshow any significant differences in SE nor gen was added to the inspirate. Table 3 a significant increase in the number of shows the distribution of periodic breathawakenings compared with studies at ing in different sleep stages. Periodic 4,572 m (429 mm Hg). breathing occurred during 41.3% ± 14.8070 of the night at 4,572 m, and this Sleep architecture as evidenced by the traditional sleep stages did not worsen increased to 75.2% ± 13.1% at 6,100 m, on ascent above 4,572 m (429 mm Hg), p
JAMES D. ANHOLM, A. C. PETER POWLES, RALPH DOWNEY III, CHARLES S. HOUSTON, JOHN R. SUTTON, MICHAEL H. BONNET, and ALLEN CYMERMAN With the technical assistance of Darlene Tyler
Introduction Sleep disturbances at high altitude frequently occur among climbers (1-4). Despite considerable interest in altitude physiology, only a few studies describing the extent of sleep disruption are available, and they are limited to altitudes below 4,400 m (4-8). Because climbers routinely describe worsening of sleep as altitude increases, it seems likely that there is an inverse relationship between sleeping altitude and sleep quality. There is no information available on sleep stages at the extreme altitudes (above 7,000 to 8,000 m) typically involved in Himalayan mountaineering. Periodic breathing during sleep at altitude has been known at least since the description of Mosso in 1898 (9). This breathing pattern is almost a universal finding at altitude. Lahiri and colleagues recently described periodic breathing during sleep in both Sherpas and sojourners up to 5,400 m, but these studies were limited by the difficulties imposed by the mountain environment, and no attempt was made to relate sleep stages to breathing pattern (5, 6). Periodic breathing has been thought to be a major cause of sleep-related arterial oxygen desaturation (10, 11), although others have suggested that periodic breathing during sleep in climbers may actually improve saturations during sleep (12). West and coworkers also studied periodic breathing during sleep in climbers at 6,300 m and 8,050 m on Mt. Everest, but measured arterial oxygen saturation only up to 6,300 m (13). Anecdotal reports have indicated disturbed sleep at very high altitudes, but data to support this are lacking. Poor sleep quality at sea level may adversely affect daytime mental performance and motor function (14, 15). Additionally, Hornbein and colleagues have recently drawn attention to central nervous system abnormalities in climbers or subjects
SUMMARY Frequent sleep disturbances and desaturatlon during sleep are common at high altitude, but few data are available from the highest altitudes at which humans are known to sleep. Because sleep fragmentation at low altitude may Impair mental function and oxygen deprivation produces lasting central nervous system abnormalities, a better understanding of the sevarlty of sleep disturbances and oxygen desaturatlon at extreme altitudes Is Important. The purpose of this study was to determine the severity of sleep disturbance and the extent of arterial oxygen desaturatlon at extreme simulated altitude. Out of eight healthy male subject volunteers who started, five aged 27.2 ± 1.5 yr completed the stUdy during 6 weeks of progresslva hypobaric hypoxia In a decompression chamber. The men were studied at barometric pressures of 760, 429, 347, 282 mm Hg and following return to 760 mm Hg. All demonstrated frequent nighttime awakenings (37.2 awakenings per subject per night at 282 mm Hg, decreasing significantly to 14.8 on return to sea level, p < 0.05). Total sleep time decreased from 337 ± 30 min at 760 mm Hg to 167 ± 44 min at 282 mm Hg (p < 0.01). Rapid eye movement (REM) sleep decreased from 17.9% ± 6.0% of sleep time at sea level to 4.0% ± 3.3% at 282 mm Hg (p < 0.01). Sleep continuity as reflected by brief arousals Increased from 22 ± 6 arousals per hour of sleep at sea level to 161 ± 66 arousals per hour at 282 mm Hg (p < 0.01). All subJects showed arterial oxygen desaturatlon proportional to the altitude. The average oxygen saturation (Sa0 2 ) was 79% ± 3% at 429 mm Hg, 66% ± 6% at 347 mm Hg, and 52% ± 2% at 282 mm Hg. Sleep stage had only a minimal effect on Sa0 2 at any altitude. Sa0 2 was negatively correlated with brief sleep arousals, r = -0.72, P < 0.01. All subJects demonstrated periodic breathing with apneas throughout much of the night at 347 and 282 mm Hg. These data Indicate that sleep quality progressively worsens as Sa0 2 decreases despite lack of progressive changes In sleep stages at altitude. This study extends previous Information on the sevarlty of desaturation during sleep, and suggests that Improvements In oxygenation might prove beneficial In restoring consolidated sleep, possibly even Improving daytime performance. AM REV RESPIR DIS 1992; 145:817-828
with prolonged hypoxic exposure (16). Because oxygen saturation during sleep at altitude may be lower than daytime values and because severe oxygen desaturation may be an important determinant of sleep quality, we sought to determine the extent of sleep impairment and oxygen desaturation at extreme simulated altitude. The primary purpose of this study was to determine whether progressive changes in sleep quality occurred assimulated altitude increased and whether these sleep changes were related to arterial oxygen saturation (Sao.). Methods Subjects Eight healthy male subjects aged 26.8 ± 3.0 yr were studied during a 40-day exposure to increasing hypobaric hypoxia. Eight healthy volunteers were invited from among 30 applicants to serve as subjects; selection was
based on motivation, personality, interest in physiology, fitness, and sports. The subjects' characteristics and other aspects of this study have been described in detail elsewhere (17). Each participant signed an informed consent
(Receivedin originalform December 14, 1990and in revised form June 10, 1991) 1 From the Department of Medicine, Lorna Linda University, Lorna Linda, California, the Department of Medicine, Cardiorespiratory Unit, McMaster University Medical Center, Hamilton, Ontario, Canada, and the Altitude Research Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. 2 Supported in part by U.S. Army Research and Development Command Contract DAMDI7-85-C5206, and by the Arctic Institute of North America. 3 Correspondence and requests for reprints should be addressed to James D. Anholm, M.D., Jerry L. Pettis Memorial Veterans' Hospital, Pulmonary Section (11IP), 11201 Benton Street, Lorna Linda, CA 92357.
817
818
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Days in Chamber Fig. 1. The ascent profile of the study showing the times spent at each altitude. Nights during which sleep studies were performed are indicated by solid squares (.). During the later part of ascent, on multiple occasions sleeping altitude was lower than the daytime altitude. When this occurred, sleeping altitude is indicated by open circles (0). During the last 7 days at altitude, one or more subjects were taken to the "summif' at the quivalent of 8,848 m for daytime studies, as indicated by arrows pointing upward. During this period, subjects not undergoing sleep studies slept at ICAO altitudes of 7,000 to 7,300 m, whereas subjects having sleep studies performed slept at 282 mm Hg (7,620 m).
at the beginning of the study, and the studies were approved by the human subjects committees of the various participating institutions. Only two subjects had had extensive altitude climbing experience, one to 7,000 m and the other to 6,000 m. None had been above 2,000 m in the 6 months prior to the study. The studies were performed in the decompression chamber ofthe U.S. Army Research Institute of Environmental Medicine, Natick, MA. The subjects lived continuously in the chamber, which was gradually decompressed to simulate ascent to altitude. The ascent profile indicating the altitudes at which sleep studies were performed is shown in figure 1. All subjects reported good nocturnal sleep prior to this study. Five subjects completed all of the sleep studies. Subject 6 refused further sleep studies above 429 mm Hg. Subject 7 had to be removed from the chamber because of a brief hypoxic episode after reaching 380 mm Hg and thus was only studied at sea level and at 429 mm Hg. Subject 5 was removed from the chamber for a brief hypoxic reaction at 282 mm Hg prior to the sleep study at this altitude. Subjects 5 and 7 experienced transient loss ofconsciousness and/or slurred speech or impaired motor function. All impairment was temporary, and both men fully recovered on descent to sea level. The data reported here, unless otherwise indicated, include the five subjects who completed all studies.
Sleep Studies The decompression chamber consisted of a living area and a smaller study chamber connected by an airlock. Chamber temperature, relative humidity, and FI02 were monitored and kept between 18to 22° C, 50 to 80% and at 1'\J20.9OJo, respectively(17). Altitude equivalents were obtained from the Manual of the ICAO Standard Atmosphere (18).Sleep stud-
ies weredone at the followingbarometric pressures and equivalent ICAO [International Civil Aviation Organization] altitudes: 760 mm Hg (sea level), 429 mm Hg (4,572 m), 347 mm Hg (6,100m), 282 mm Hg (7,620 m), and again following descent to sea level. Above 282 mm Hg the relationship between barometric pressure and altitude differs increasingly from that predicted by the ICAO pressure-altitude curve (19,20). Thus, 282 mm Hg is approximately 8,000 m on Mt. Everest, but corresponds to an ICAO altitude of only 7,620 m. Standard sleep recordings weremade using electrodes for monitoring the central electroencephalogram (EEG) (C3-A2 and/or C 4 At) as well as electrodes attached above or below the outer canthus of each eye for detecting rapid eye movement (REM) sleep. All EEG data and respiratory data from an inductance system wererecorded on a polygraph (ModeI8-IOBC; Grass Instruments, Quincy, MA). In addition, arterial oxygen saturation (Sao 2) by ear oximeter (Model 47201A; Hewlett-Packard, Palo Alto, CAl and the electrocardiogram (ECG) wererecorded continuously throughout the night. Chest and abdominal respiratory excursions weremonitored using an inductance system (Respitrace'"; Ambulatory Monitoring, Ine., Ardsley, NY). This inductance system was used uncalibrated but adjusted to give good abdominal and rib-cage signals. Minute ventilation was measured by having subjects wear a soft, close-fitting face mask (Downs CPAP mask; Vital Signs, Totowa, NJ) with a pneumotachograph attached to the inspiratory port. This pneumotachograph was calibrated at the study altitude using a l-L syringe at various flow rates before and intermittently during each night's studies. The mask allowed the addition of oxygen, carbon dioxide, or nitrogen to the inspired air to perform the ventilatory response studies, which
will be reported separately. During the time at altitude, no alcoholic beverages, caffeine, or other drugs known to alter sleep were consumed by any of the subjects prior to their sleep study. Acetaminophen was used to treat altitude-related headaches. The subjects were studied in pairs for the entire night. While they slept, supplemental oxygen, nitrogen, or carbon dioxide was administered to them intermittently throughout the night to assess ventilatory responses to hypoxia and hypercapnia. These responses were of varying lengths; however, the total time occupied by the responses was usually less than 25% ofthe night. All data from the control of breathing studies wererecorded on separate strip chart recorders from the sleep polygraph. Sleep recordings were made at a paper speed of 15mm/s (20-sepochs) throughout the night. Sleep stages werescored according to Rechtschaffen and Kales (21)by an experienced sleep technician. Definitions and formulas used in calculating sleep variables are as follows: total sleep time (TST) is the total number of minutes of Stages 1,2, 3, 4, REM, and movement time. The percentage of time in any sleep stage is calculated from the number of minutes of that sleep stage divided by the sum of TST plus any time spent awake during the night after the first occurrence of Stage 1. Total time in bed (TIB) is the total time from the start to finish of recording, regardless of whether the subject was awake or asleep. Sleep efficiency (SE) equals TST divided by TIB. A nighttime awakening is defined as art awake EEG pattern for one half or more of the standard epoch (i.e, 10 s or more). An arousal is a brief (2 to 10s) EEG disturbance consisisting of the appearance of alpha activity, a stage change, and evoked K-complex, EEG speeding (a clearly noticeable increase in EEG frequency overthe previous frequency), or movement (14,15,22,23). These arousals are not scored as awakenings, and subjects typically do not remember most of the arousals on awakening in the morning. Above Sao, readings of 50%, the HewlettPackard oximeter readings correlate wellwith arterial blood samples, but below 50% Sao 2, the oximeter significantly underestimates saturation (24).We developed a specificcorrelation factor by matching the measured arterial blood Sao2 values to simultaneous oximeter values during the daytime Operation Everest II studies. Using this factor, true Sao, = (oximeter reading + 19)/1.2 over the entire range of Sao, values (25). This equation was developed from a subset of the data of Forte and colleagues (25). It givessimilar, but not identical, values to that of Forte's equation. This formula also givessomewhat different values than does the correction suggested by Douglas and coworkers (24) that below 50% San, the true Sao, = observed Sao, + 'i'2(50 - observed Sao2). The average arterial oxygen saturation in each sleep stage was determined by adding the average saturation during each minute in a particular stage and dividing by the time in minutes in that stage. The time occupied
SATURATION AND SLEEP AT ALTITUDE
by the ventilatory response tests and an additional 4 min after resumption of breathing room air following chemosensitivity testing was excluded from this analysis. Periodic breathing as used here refers to a repetitive cyclicrespiratory pattern with or without apnea. Apnea is the cessation of breathing for a period of 10 s or longer, characterized by the absence of respiratory movement on the respiratory tracing. Apneas may be of two types, central or obstructive. Central apnea refers to those apneas characterized by an absence of respiratory movement of the chest wall as well as the absence of air flow. Obstructive apnea refers to those apneas in which air flow is obstructed in the upper airway but respiratory efforts continue, as evidenced by chest-wall movement during the apnea. No obstructive apneas were observed in this study. The term respiratory pause refers to a cessation of the normal breathing pattern for less than 10 s. The sleep-stagedata wereanalyzed by analysis of variance for repeated measurements for changes in the percent time in each stage at each altitude (26). Post hoc analysis using Newman-Keulscomparisons weremade when appropriate. A p value of less than 0.05 was considered significant.
Results
Altitude Effects on Sleep All subjects complained to some degree of poor sleep throughout the Operation Everest II study. These complaints were primarily difficulty falling asleep, frequent nighttime awakenings, and feeling less refreshed in the morning than expected. Some of these complaints were unrelated to altitude but due to the monitoring equipment and conditions of the sleep studies. Sleep difficulties were present in some subjects even on nights when sleep recordings were not done. Sleep variables are presented in table 1. Because it was not possible to study all subjects on their first night at each altitude, table 1 also shows the number of days acclimatizing prior to the sleep study. At sea level prior to ascent, subjects were awake 9.5070 ± 7.8% of the night, compared with 1.3% of the night that has previously been reported in normal young adults. Similarly, slow-wave sleep was reduced from what would be normally expected for healthy young adults. Time awake increased from 9.5% ± 7.8% of the night at sea level 41.1% ± 15.7070, 25.2070 ± 10.1070, and 45.8070 ± 21.2% at 4,572 m, 6,100m, and 7,620 m, respectively (p < 0.05 sea level compared with 4,572 m, and 7,620 m). Likewise, REM sleep was reduced from 17.9070 ± 6.0070 of the night at sea levelto 5.4070 ± 1.6070, 9.2070 ± 2.2%, and 4.0% ± 3.3070 at 4,572 m, 6,100 m, and 7,620 m, respec-
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tively (p < 0.05 sea level compared with 65.5 at 7,620 m (282 mm Hg). Brief 4,572 m, 6,100 m, and 7,620 m). On re- arousals were highly negatively correlatturn to sea level, REM sleep increased ed with arterial oxygen saturation, r = relative to nights at altitude, with REM - 0.72, p < 0.01. now occupying 20.1070 ± 5.9% of the Two further indices of sleep quality night in REM sleep. shown in table 2 are the Top 1 and Top Slow-wave sleep (Stages 3 + 4) oc- 5 intervals. These numbers refer to the cupied 6.8070 ± 3.6% of the night at sea longest and the fifth longest arousal-free level compared with the normal value of interval per 100arousals and serve as an approximately 21070 ± 5070 (27). Slow- indication of the distribution of arousalwave sleep remained the same during al- free sleep periods. The Top 5 intervals titude exposure (3.7070 ± 6.3070, p = NS), decreased from 11.9 ± 3.1 min at sea level then increased to 10.6070 ± 8.6% follow- to 5.1 ± 3.6 min at 4,572 m, 4.0 ± 3.1 ing return to sea level. min at 6,100 m, and 1.5 ± 0.9 min at Since hypoxic and hypercapnic ventila- 7,620 m. Other values for Top 1 are inditory response testing during the night cated in the table. Thus, a Top 1 value may have interfered with sleep, the of 7.2 min at 7,620 m indicates that the changes in sleep stages were reanalyzed longest period of undisrupted sleep was after excluding this time (f\J20% of TIB). only 7.2 min. This analysis indicated that chemosensiAltitude Effects on Breathing tivity testing disrupted sleep by signifiand Saturation cantly increasing nighttime awakenings at sea level and 6,100 m (347 mm Hg). At and above 4,572 m (429 mm Hg), all Additionally, this testing reduced Stage subjects showed periodic breathing with 3 sleep from 2.0070 ± 0.9% to 1.1 ± 0.6070 apneas during the night. All apneas and at 6,100 m (347 mm Hg), but also de- respiratory pauses at all altitudes studcreased movement time at 6,100 m. No ied were central, because when no airother significant differences were found. flow occurred at the mouth, there was The TIB during the night was the same no chest or abdominal movement. Periat all altitudes. The equipment worn by odic breathing with or without apneas the subjects and the hypoxic and hyper- occurred in all subjects prior to ventilacapnic ventilatory response testing was tory response testing. Apneas were elimsimilar at all altitudes. These ventilatory inated when supplementary oxygen was responses had very little overall effect on administered, but periodic breathing persleep stages. Thus, the altitude-related sisted (figure 2). Apneas reappeared soon changes in sleep stages and TST were not after return to ambient air (figure 3). Addue to alterations in time available for . dition of 2 to 4070 carbon dioxide to the sleep or monitoring equipment worn, but inspired gas mixture also eliminated aprather to the sleep disruption that the sub- neas, even though fluctuation in tidal voljects experienced. ume remained (figure 4). Periodic breathSleep continuity deteriorated at alti- ing produced an oscillation in Sa02 of tude, as evidenced by SE (TST/TIB) and 6.6 ± 1.9%. There was no significant the number of awakenings compared difference in the fluctuation of Sa02 at with sea level. SE was 88.6070 ± 8.2070 different altitudes. At the highest altiat sea level and 55.5070 ± 15.5070 at tudes studied, the subjects reported con4,572 m (429 mm Hg), p < 0.05. Sleep siderable difficulty sleeping, but would studies at 6,100 m and 7,620 m did not promptly fall asleep when low-flow oxyshow any significant differences in SE nor gen was added to the inspirate. Table 3 a significant increase in the number of shows the distribution of periodic breathawakenings compared with studies at ing in different sleep stages. Periodic 4,572 m (429 mm Hg). breathing occurred during 41.3% ± 14.8070 of the night at 4,572 m, and this Sleep architecture as evidenced by the traditional sleep stages did not worsen increased to 75.2% ± 13.1% at 6,100 m, on ascent above 4,572 m (429 mm Hg), p
