Abstract
Rationale: Quantitative data on ventilation during acclimatization at very high altitude are scant. Therefore, we monitored nocturnal ventilation and oxygen saturation in mountaineers ascending Mt. Muztagh Ata (7,546 m).
Objectives: To investigate whether periodic breathing persists during prolonged stay at very high altitude.
Methods: A total of 34 mountaineers (median age, 46 yr; 7 women) climbed from 3,750 m within 19–20 days to the summit at 7,546 m. During ascent, repeated nocturnal recordings of calibrated respiratory inductive plethysmography, pulse oximetry, and scores of acute mountain sickness were obtained.
Measurements and Main Results: Nocturnal oxygen saturation decreased, whereas minute ventilation and the number of periodic breathing cycles increased with increasing altitude. At the highest camp (6,850 m), median nocturnal oxygen saturation, minute ventilation, and the number of periodic breathing cycles were 64%, 11.3 L/min, and 132.3 cycles/h. Repeated recordings within 5–8 days at 4,497 m and 5,533 m, respectively, revealed increased oxygen saturation, but no decrease in periodic breathing. The number of periodic breathing cycles was positively correlated with days of acclimatization, even when controlled for altitude, oxygen saturation, and other potential confounders, whereas symptoms of acute mountain sickness had no independent effect on periodic breathing.
Conclusions: Our field study provides novel data on nocturnal oxygen saturation, breathing patterns, and ventilation at very high altitude. It demonstrates that periodic breathing increases during acclimatization over 2 weeks at altitudes greater than 3,730 m, despite improved oxygen saturation consistent with a progressive increase in loop gain of the respiratory control system.
Clinical trial registered with www.clinicaltrials.gov (NCT00514826).
Data on the breathing pattern and ventilation during acclimatization over the course of several weeks at very high altitude are scant.
This field study in mountaineers climbing to high altitude demonstrates that nocturnal periodic breathing increases during acclimatization over the course of more than 2 weeks at altitudes between 3,750 m and 6,850 m, despite improving oxygen saturation and independent of manifestations of acute mountain sickness. These data shed light on the pathophysiology of periodic breathing, and understanding of high-altitude tolerance and illness.
Subject recruitment and baseline characteristics have been published previously (11). Briefly, healthy, physically fit mountaineers with current regular mountaineering practice and previous climbing experience, including several climbs and ski tours in the high Alps over the previous few years, were considered for participation. Subjects were excluded if they required regular intake of medication, had previous severe high altitude–related illness at altitudes below 3,500 m, or if the medical history, physical examination, spirometry, or spiroergometry revealed evidence of any medical condition. A total of 35 volunteers were recruited, and gave written, informed consent to the study, which was approved by the Ethics Committee of the University Hospital of Zurich. One volunteer had to return home before reaching the base camp because of severe traveler's diarrhea. Therefore, 34 mountaineers (median age, 46 [range, 26–65] yr; 7 women) participated in the study. They had a normal spirometry and were physically very fit, as reported previously (11).
Evaluations included a physical examination and assessment of acute mountain sickness (AMS) by the environmental symptoms questionnaire cerebral (AMS-c) score (16). Nocturnal polygraphic recordings were obtained by a lightweight (450 g), portable monitoring system (LifeShirt; VivoMetrics, Ventura, CA) that we had extensively validated in terms of accuracy of derived tidal volumes, apnea/hypopnea counts, and robustness during field studies (14, 15, 17, 18). The device consists of an individually adjusted, snugly fitting body garment, the LifeShirt, with built-in respiratory inductance plethysmography sensors encircling the rib cage and the abdomen. Pulse oximetry by a finger sensor, ECG, and four accelerometers for detection of movements and body position are also incorporated. Accuracy of the pulse oximeter (Xpod, Nonin Medical, Plymouth, MN) is ±2% in the range of 70–100%, according to the manufacturer's specifications. In addition, accuracy over the entire relevant range of 100–40% oxygen saturation as measured by pulse oximetry (SpO2) was verified by means of a calibrator-simulator (CardioSat 100 SpO2 simulator; DNJ Nevada Inc., Carson City, NV) (see Figure E1 in the online supplement).
The inductance signals were calibrated in the evening by the qualitative diagnostic calibration procedure and by subsequent comparison to the known volume (0.8 L) of a bag into which subjects rebreathed for 4–8 breaths while in the supine position (15, 19). Accuracy of calibration was verified in the morning, and was regarded as acceptable if inductive plethysmographic tidal volumes were within 20% of calibration bag volume. This was the case in 136 of 209 recordings, with a mean deviation between evening and morning calibration of 2%. In 73 recordings, bag calibration was available either in the evening or in the morning only, as subjects had not performed both calibration maneuvers, so that accuracy could not be validated. In 12 recordings, recalibration revealed a deviation of greater than 20% from bag volume. Tidal volume and minute ventilation values from these recordings were discarded and replaced by the corresponding median value of the group. Signals were continuously recorded on a new flash memory card inserted in the LifeShirt monitor before each overnight recording. Data cards were downloaded into a computer after return to the base camp. LifeShirt monitors were powered by batteries allowing up to 24 hours of continuous recordings. Batteries were recharged during daytime by generators available at each high camp.
Climbers were randomly assigned to one of two groups ascending with different protocols, but the total duration of the trip was 5 weeks for both (11). Baseline evaluation was performed in Zurich (490 m) within 4 weeks before departure. Climbers flew from Zurich to Islamabad, Pakistan, and subsequently traveled by bus on the Karakorum Highway for 5 days. Starting from Subash (3,730 m, Day 1), located at the base of Mt. Muztagh Ata, climbers followed two different ascent protocols, as depicted in Figure 1, and as reported previously (11). Ascent at altitudes greater than 4,800 m was on snow and performed with mountaineering skis. Participants carried their personal equipment and were led by experienced mountain guides, who assured that climbing rate did not exceed 1,036 m/d within 6–8 hours, and was maintained as similar in both groups. No medication known to alter control of breathing, such as acetazolamide, theophylline, aspirin, or benzodiazepines, were allowed. Subjects unable to proceed with their group as planned because of exhaustion or high altitude–related illness, or who required any medication other than just pain killers (paracetamol or ibuprofen), were accompanied to lower altitude at the earliest occasion and received treatment as needed.
Figure 1. Protocol of the expedition to Mt. Muztagh Ata. After traveling on the Karakorum highway from Islamabad to Subash (reached on Day 1 in this plot), two groups of 18 and 16 mountaineers, respectively, ascended with different protocols. Closed and open circles represent overnight stays of the fast and slow groups, respectively, in a camp. The fast group reached higher altitudes earlier until Day 14, when bad weather forced the group to deviate from the predefined protocol (dashed line) and descend to base camp. The group resumed ascent on Day 16, and 9 of the 18 mountaineers reached the summit on Day 20. The slow group ascended as planned, and 8 of the 16 mountaineers reached the summit on Day 19. The number of subjects in each group ascending to and beyond a certain point is indicated within circles (fast group) and rectangles (slow group) on the lines representing the corresponding ascent. The letters F and S indicate the time of nocturnal breathing pattern recordings in the fast and slow groups, respectively.
[More] [Minimize]Polygraphic recordings were performed during the nights marked on the ascent profile shown in Figure 1. The equipment was mounted in the evening within tents before subjects went to sleep. The respiratory inductive plethysmograph was calibrated when subjects were supine in sleeping bags before and after the nocturnal rest (generally between 7–9 p.m. and 5–7 a.m.). Time stamps identifying the nocturnal rest period were recorded in the LifeShirt monitor.
Polygraphic recordings were analyzed by dedicated software (VivoLogic; VivoMetrics) (17). Timing, volume, and flow components of breathing patterns were obtained breath by breath, along with SpO2 and heart rate. Mean values for the nocturnal rest period identified by time stamps were computed. Apnea/hypopnea were scored if the inductive plethysmographic sum volume signal was reduced to less than 50% for 10 seconds or more in comparison to the preceding 2-minute baseline (20, 21). Transient reductions in breathing amplitude to less than 50% baseline over 5–10 seconds were also scored as apneas/hypopneas if they occurred as part of a periodic breathing pattern with waxing and waning of ventilation with periods of hyperventilation alternating with central apneas/hypopneas over at least three successive cycles. Central apneas/hypopneas were identified by absence of rib cage–abdominal asynchrony. The apnea/hypopnea index and the oxygen desaturation index (≥4% dips) were defined as the number of events per hour. The lung-to-finger circulation time was measured from the onset of a hyperventilatory phase of periodic breathing to the corresponding rapid rise in SpO2 (22).
Results are summarized by medians (quartiles), because most outcome variables were not normally distributed. Changes over time were evaluated by Kruskal-Wallis analysis of variance and by Mann-Whitney U tests, or by Wilcoxon matched pairs tests, as appropriate. Potential determinants of the apnea/hypopnea index and percent time with periodic breathing were evaluated by univariate and multivariate random effects ordinal logistic regression (23). A probability of P less than 0.05 was considered statistically significant.
A total of 18 climbers (median age, 46 [range, 26–65] yr; 3 women) were randomized to the fast ascent group, and 16 climbers (median age, 46 [range, 29 to 57] yr; 4 women) to the slow ascent group. Baseline characteristics of the groups were similar, as previously described (see Table 1 in Reference 11). A total of 9 of the 18 climbers of the fast group reached the summit on Day 20, whereas the other 9 climbers returned to base camp prematurely at various time points (Figure 1) due to symptoms of AMS or exhaustion. Average ascent rate from Subash (3,730 m, Day 1) to camp II (6,265 m, Day 12) was 211 m/d, and, during the final ascent from base camp (4,497 m, Day 17) to the summit (7,546 m, Day 20), it was 762 m/d. A total of 8 of the 16 climbers of the slow-ascent group reached the summit, whereas 8 returned prematurely because of symptoms of AMS or exhaustion (Figure 1). The average ascent rate from Subash to camp II (6,265 m on Day 16) was 158 m/d, and it was 508 m/d during the final ascent from base camp to the summit on Days 14–19. All participants of the expedition returned home safely and in good health.
Location | Zurich | Base Camp | Camp I | Base Camp | Camp I | Camp II | Camp III | P Value* |
|---|---|---|---|---|---|---|---|---|
| Altitude, m | 490 | 4,497 | 5,533 | 4,497 | 5,533 | 6,265 | 6,865 | |
| ft | 1,608 | 14,754 | 18,153 | 14,754 | 18,153 | 20,554 | 22,523 | |
| PB, mm Hg | 706 | 594 | 521 | 594 | 521 | 474 | 438 | |
| Day | ||||||||
| fast group | 4 | 6 | 9 | 11 | 13 | 19 | ||
| slow group | 5 | 7 | 13 | 15 | 17 | 18 | ||
| No. of subjects | 34 | 33 | 33 | 32 | 29 | 24 | 24 | |
| Nocturnal rest, min | 392 (361, 447) | 488† (474, 522) | 672†‡ (617, 707) | 525† (473, 608) | 635†‡ (600, 675) | 637†‡ (591, 707) | 492†‡ (452, 520) | <10−3 |
| SpO2, % | 95 (94, 96) | 79† (75, 80) | 69†‡ (66, 73) | 83†§ (82, 85) | 74†‡§ (71, 76) | 66†‡ (63, 70) | 64†‡ (61, 67) | <10−3 |
| Breath rate, 1/min | 14.8 (13.5, 16.6) | 17.6† (16.3, 19.7) | 18.6†‡ (17.6, 20.6) | 17.0† (15.7, 18.2) | 18.2†‡ (17.3, 19.3) | 18.8†‡ (17.7, 21.4) | 20.5†‡ (19.2, 22.5) | <10−4 |
| Vt, L | 0.31 (0.25, 0.39) | 0.34 (0.29, 0.41) | 0.38† (0.34, 0.43) | 0.39† (0.32, 0.59) | 0.43† (0.35, 0.60) | 0.49†‡ (0.39, 0.63) | 0.50†‡ (0.43, 0.63) | <10−4 |
| V̇e, L/min | 4.9 (3.6, 5.7) | 6.5† (5.0, 8.0) | 7.3† (6.3, 8.2) | 6.7† (5.5, 10.2) | 7.9†‡ (6.4, 11.5) | 9.5†‡ (8.0, 11.6) | 11.3†‡ (9.6, 13.9) | <10−4 |
| Circulation time, s | NA | 17.4 (15.3, 19.0) | 12.6‡ (11.7, 14.5) | 18.3 (17.0, 20.2) | 13.8‡ (12.5, 15.4) | 11.6‡ (10.6, 12.4) | 10.4‡ (9.7, 12.3) | <10−3 |
| Heart rate, 1/min | 54 (51, 60) | 67† (59, 76) | 66† (61, 76) | 58§ (53, 61) | 64†‡ (60, 67) | 67†‡ (64, 76) | 72† (66, 86) | <10−4 |
| AMS-c score | 0.00 (0.00, 0.00) | 0.00† (0.00, 0.18) | 0.17†‡ (0.00, 0.273) | 0.00 (0.00, 0.00) | 0.00§ (0.00, 0.09) | 0.09†‡ (0.00, 0.25) | 0.31†‡ (0.00, 0.47) | <10−4 |
The polygraphic equipment was well tolerated by the climbers, and proved to be easy to use and very robust under the challenging field conditions of the expedition. All devices worked properly until the end of the expedition. A total of 209 overnight recordings were successfully obtained. A total of 12 additional scheduled or attempted recordings were not available: 8 because the equipment could not be carried in time to the camp where it was needed, and 4 because of technical failure (premature loss of battery power). Therefore, and because several climbers gave up the ascent prematurely, the number of polygraphies performed over the course of the ascent varied. A representative recording obtained at 6,850 m is shown in Figure 2.
Figure 2. Nocturnal polygraphic recording obtained at 6,850 m in a 29-year-old woman. The channels are the respiratory inductive plethysmographic sum, rib cage and abdominal volume, V̇e, heart rate, and oxygen saturation as measured by pulse oximetry (SpO2). In the first part of the 3-minute recording, breathing is regular. Subsequently, periodic breathing is triggered by a large breath (sigh or gasp). This results in oscillations of SpO2 from 64 to 71%.
[More] [Minimize]Nocturnal breathing pattern variables, SpO2, and heart rate are summarized, along with AMS-c scores, in Tables 1 and 2 for both groups combined, because the differences between groups at corresponding altitudes were minor (individual group data are provided in Tables E1–E4). There was a significant trend toward a decrease in SpO2 with increasing altitude (Table 1 and Table E5), whereas minute ventilation at 6,865 m reached more than twice the baseline value at 490 m. This was due to an increase in both tidal volume and breath rate (Figure 3). The increase in heart rate at higher altitude was associated with a decrease in circulation time. To evaluate the effect of acclimatization, repeated recordings obtained at the same altitudes (i.e., during the first and second stay at base camp and camp I, respectively) were compared (Tables 1 and 2). This analysis revealed a significant increase in SpO2 with acclimatization at both altitudes, whereas the increase in minute ventilation was not statistically significant.
Figure 3. Medians of volume and timing components of breathing patterns measured during nocturnal polygraphies. The lines connect beginning of inspiration (time = 0 s; volume = 0 L) with maximal inspiration/beginning of expiration and end of expiration (time > 0 s; volume = 0 L). Numbers within symbols represent the order of examinations over the course of the expedition (see also Figure 1). With increasing altitude and time, tidal volume (value on y axis) increases, and respiratory cycle time (value on x axis) decreases. The slope of the lines starting at time 0 and volume 0 reflects mean inspiratory flow, a measure of respiratory drive, which is progressively increasing with altitude and time.
[More] [Minimize]Location | Zurich | Base Camp | Camp I | Base Camp | Camp I | Camp II | Camp III | P Value* |
|---|---|---|---|---|---|---|---|---|
| Altitude, m | 490 | 4′497 | 5′533 | 4′497 | 5′533 | 6′265 | 6'865 | |
| ft | 1′608 | 14′754 | 18′153 | 14′754 | 18′153 | 20′554 | 22′523 | |
| PB, mm Hg | 706 | 594 | 521 | 594 | 521 | 474 | 438 | |
| Day | ||||||||
| fast group | 4 | 6 | 9 | 11 | 13 | 19 | ||
| slow group | 5 | 7 | 13 | 15 | 17 | 18 | ||
| N subjects | 34 | 33 | 33 | 32 | 29 | 24 | 24 | |
| AHI, 1/h | 4.0 (1.2, 9.7) | 30.4† (20.0, 64.2) | 110.1†‡ (75.3, 130.4) | 71.9†§ (37.2, 96.2) | 114.1†‡ (81.1, 130.3) | 142.6†‡ (120.4, 154.2) | 132.3†‡ (103.3, 157.4) | <10−3 |
| Periodic breathing, % time | NA | 21 (12, 40) | 63‡ (42, 81) | 56§ (27, 69) | 71‡ (52, 84) | 85‡ (65, 90) | 69‡ (56, 86) | <10−3 |
| Cycle time, s | NA | 23.1 (21.4, 27.3) | 21.4‡ (18.8, 24.0) | 26.1§ (23.7, 30.0) | 23.1§ (20.1, 25.0) | 20.0‡ (18.8, 22.6) | 19.6‡ (17.3, 20.0) | <10−4 |
| Minimal SpO2, % | NA | 76 (71, 78) | 67‡ (61, 70) | 80§ (78, 82) | 70‡§ (68, 72) | 62‡ (60, 66) | 60‡ (55, 63) | <10−3 |
Table 2 contains summary statistics of transient nocturnal respiratory events. Baseline studies in Zurich (490 m) revealed normal values of the apnea/hypopnea index (21). At base camp and in the high camps (I–III), the mountaineers spent most of the night with periodic breathing. The apnea/hypopnea index increased with increasing altitude, and reached very high values of 98.8/h to 151.6/h at the high camps. Correspondingly, the cycle time of periodic breathing became progressively shorter and reached the lowest value of 19.6 seconds at camp III. Periodic breathing was associated with large oscillations in SpO2, with nadirs as low as 60–62% at camps II and III (Table 2, Figure 2).
During the second stay at base camp (4,497 m) and at camp I (5,533 m), respectively, the apnea/hypopnea index and the time spent with periodic breathing had increased compared with the first time, although this trend was significant at base camp only (Table 2). Figure 4 illustrates the trend of the increasing apnea/hypopnea index with increasing altitude and over time during the expedition. To further explore the hypothesis that periodic breathing increased with prolonged acclimatization at altitude, ordinal logistic regression analysis was performed. The quartiles of the apnea/hypopnea index were entered as the dependent variable and acclimatization time (days spent above Subash, 3,750 m) as the independent variable, with mean nocturnal SpO2, altitude, group membership (fast or slow), deviation from the predefined ascent protocol by the fast group (Figure 1), AMS score, age, and sex as potential confounders. The analysis revealed that acclimatization time was highly significantly and positively correlated with the apnea/hypopnea index in univariate analysis (Table E6) and in multivariate analysis that controlled for other, potentially confounding, independent variables, including AMS-c scores (Table 3). A similar analysis with the percent of the night-time spent with periodic breathing as the dependent variable also confirmed a significant positive effect of acclimatization time on periodic breathing when controlling for confounding variables (Table 3).
Figure 4. Apnea/hypopnea index over the course of the expedition. The bars and vertical lines represent medians and quartile ranges. *P < 0.001 versus all lower locations; **P < 0.001 versus all lower locations except 6,265 m; ¶P < 0.01 versus first stay at 4,497 m and versus 490 m; †P < 0.001 versus 490 m.
[More] [Minimize]AHI, 1/h* | % of Night with Periodic Breathing† | |||||
|---|---|---|---|---|---|---|
| Determinants | Beta Coefficient (95% CI) | P Value | Beta Coefficient (95% CI) | P Value | ||
| Acclimatization time (d above 3,750 m) | 0.15 (0.05 to 0.25) | 0.003 | 0.17 (0.05 to 0.28) | 0.005 | ||
| SpO2, % | −0.12 (−0.23 to −0.01) | 0.028 | −0.09 (−0.19 to 0.02) | 0.116 | ||
| Altitude, m | 5.1 (−6.8 to 17.0) × 10−4 | 0.400 | 1.7 (−11.2 to 14.4) x10−4 | 0.798 | ||
| Group (fast = 1; slow = 2) | −1.64 (−2.85 to −0.44) | 0.008 | −2.03 (−3.14 to −0.92) | <0.001 | ||
| Protocol deviation (none = 0, deviation = 1) | −1.39 (−2.49 to −0.29) | 0.013 | −1.87 (−3.02 to −0.73) | 0.001 | ||
| AMS-c score | 0.16 (−1.26 to 1.58) | 0.820 | −0.23 (−1.68 to 1.23) | 0.757 | ||
| Age, yr | 0.027 (−0.024 to 0.077) | 0.305 | 0.049 (−0.001 to 0.099) | 0.056 | ||
| Sex (male = 1; female = 2) | 0.75 (−0.87 to 2.37) | 0.365 | 0.16 (−1.11 to 1.43) | 0.801 | ||
We studied the nocturnal breathing pattern, SpO2, and heart rate in a large cohort of healthy mountaineers over the course of a climb to very high altitude. Unobtrusive recordings by a portable device incorporating calibrated respiratory inductive plethysmography revealed that minute ventilation increased with progressive hypoxemia at increasing altitude and with elapsed time over the course of the ascent. The highest minute ventilation measured at 6,850 m was more than twice of that at 490 m. Periodic breathing emerged in all high camps, and prevailed for the major part of the night at altitudes of 5,533 m and higher. The increase in the apnea/hypopnea index during repeated recordings at 4,497 m and multiple regression analysis suggest that periodic breathing increases during prolonged acclimatization of more than 2 weeks at high altitude (>3,730 m), and is not related to symptoms of AMS. Our observations provide new insights into ventilatory acclimatization to very high altitude that may facilitate a better understanding of high-altitude tolerance and related illness. Our data further demonstrate that the portable device (the LifeShirt) for monitoring of ventilation was well tolerated and robust enough to be used as a valuable tool in the challenging conditions of high-altitude field studies.
Previous studies on high-altitude periodic breathing found apnea/hypopnea indices between 10/h and 54.1/h at 2,650–3,840 m (7, 10, 24–27) and between 47.1/h and 96.0/h at 4,000–5,050 m (4, 25, 28–32). The percent of the night with periodic breathing was 18–34% (7, 27, 33) at 3,450–3,700 m and 34–80% at 4,000–4,572 m (7, 28, 29, 31). The large variation in reported values may relate to differences in study design and setting (i.e., field studies [7, 24, 27, 31, 32]) versus hypobaric chamber studies (10, 25, 28), acclimatization time, and the small sample size of most studies (5–21 subjects). Nevertheless, an increase in the prevalence of periodic breathing with increasing altitude up to 5,050 m was a consistent finding. Our study demonstrates that this trend goes on at altitudes of 4,497 m and up to 6,850 m (Table 2 and Figure 4).
Data on nocturnal breathing patterns at altitudes greater than 5,050 m are very scant. West and coworkers (6) monitored the breathing pattern of eight subjects acclimatized for 17 days or more at 6,300 m on Mt. Everest at the beginning of a nocturnal rest period during 62–210 minutes. Subjects spent 73% of the time with periodic breathing, and their SpO2 varied between 73 and 63%. Five participants of operation Everest II exposed to progressive hypobaric hypoxia in a decompression chamber over the course of several weeks revealed nocturnal periodic breathing in 75% of the night-time, and the SpO2 was 78% at 6,100 m; corresponding values at 7,620 m for periodic breathing and SpO2 were 75% of the night-time and 71% (28). Because of the relatively short recording time (6) and the particular setting of a chamber simulation (28), the cited data might not be representative for entire nights in the field. The current field study, performed in a much larger sample of 32–34 subjects at altitudes up to 5,533 m, and in 24 subjects at 6,250 m and 6,850 m, demonstrates severe nocturnal hypoxemia with lowest values of the mean SpO2 of 64% at 6,850 m (Table 1). Moreover, nadirs of SpO2 related to the highly prevalent periodic breathing were even lower (i.e., 60% at 6,850 m) (Table 2). Periodic breathing prevailed during the major part of the night at 5,533 m and higher altitudes. Correspondingly, the apnea/hypopnea index increased with altitude, and the cycle time of periodic breathing became progressively shorter (Table 2). The rise in heart rate associated with a reduction of the circulatory delay that we observed with increasing altitude (Table 1) may have reduced the response time of peripheral chemoreceptors to alterations in blood gases, thereby contributing to a higher frequency of ventilatory oscillations.
Repeated recordings obtained within a few days at base camp (4,497 m) revealed an increase in the apnea/hypopnea index, despite a simultaneous increase in SpO2 (Tables 1 and 2). This finding, and the progressive rise in minute ventilation over the course of the expedition (Table 1), is consistent with an increasing gain of the respiratory feedback control system during acclimatization (9). Thus, a high ventilatory sensitivity to CO2 and hypoxia in the presence of a narrowed CO2 reserve may have promoted breathing instability with an overshooting response to apnea. Alteration in plant gain related to the major increases in tidal volume that reduced the dead space fraction, and changes in pulmonary and systemic circulation reflected in the increased heart rate and the reduced circulatory delay (Table 1), may have additionally affected the respiratory control stability. Multiple regression analysis confirmed that acclimatization time (i.e., the number of days spent above 3,750 m) was a significant determinant of periodic breathing, independent of the amount of hypoxemia, symptoms of AMS, and other confounding variables (Table 3). Thus, our data suggest that periodic breathing does not vanish, but rather increases during prolonged acclimatization at very high altitude. This is consistent with the persistence of periodic breathing observed in five subjects during 28 days at 5,050 m (8), and with another report on nine subjects showing no reduction in periodic breathing over the course of 5 days at 3,200 m, despite increasing SpO2 (10). Our results contrast with one study in five subjects, which found a reduction in periodic breathing over the course of 5 days at 4,300 m (9). However, the subjects in that study (9) were wearing a facemask and underwent hypoxic/hyperoxic and hypercapnic challenges during sleep, which may have altered their breathing pattern.
We measured ventilation by a portable respiratory inductive plethysmograph that incorporated volume sensors within an individually adjusted, snugly fitting body garment, thereby preventing sensor displacement. Extensive validations have confirmed that the device accurately estimates tidal volumes in unrestrained subjects during several hours, without requiring airway instrumentation (14, 15, 17). In the current study, corroboration of the inductive plethysmograph calibration in the morning revealed no significant bias, and accuracy of tidal volumes within 20% compared with the evening calibration in the majority of recordings. We are therefore confident that the median values derived from measurements in the different camps are accurate within these limits and reflect the physiologic trends. We observed that mean nocturnal minute ventilation increased progressively with altitude and time from 4.9 L/min at 490 m to the highest values of 11.3 L/min at 6,850 m. This was due to an increase in both tidal volume and breath rate (Table 1, Figure 3). These detailed data on ventilation at different elevations up to very extreme altitude are unique, as similar measurements have not previously been feasible. Although ventilation at altitude has been studied in the past in small numbers of subjects with a flow meter attached to a mask, such measurements may not have reflected the natural breathing pattern and ventilation because of the disturbed sleep and alterations in ventilation induced by such instrumentation (34). In particular, the added dead space associated with the use of a mask may have diminished periodic breathing (35).
In conclusion, the current study provides novel data on nocturnal SpO2 and on the breathing pattern obtained in a relatively large sample of mountaineers climbing to extreme altitude. With progressive hypoxemia at increasing altitude, minute ventilation increased in association with an increasing prevalence of central apnea/hypopnea, a shorter cycle time of periodic breathing, and a reduced circulatory delay, in accordance with predictions by respiratory control theory (36). Periodic breathing prevailed during the major part of the night at 5,533 m and higher elevations, and further increased during a prolonged stay at altitude, despite improvements in SpO2 during acclimatization, and independent of symptoms of AMS.
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