Sleep disturbances in response to acute altitude ascent are very common and well documented. Objective changes in sleep architecture were first documented by Joern et al. in 1970 in a study of two men at greater than 3000 m. in Antarctica. The study revealed a near absence of deep wave sleep, a substantial decrease in rapid eye movement (REM) sleep, and the presence of periodic breathing (PB) with associated arousals [
This study seeks to further contribute to the understanding of high-altitude sleep by focusing on PB. PB, when occurring in healthy individuals, almost universally predominates at high altitudes [
In this present study, we sought to test the hypothesis that the PB events at elevated altitude are associated with an increase in behavioral awakenings. In doing so, we hope to clarify how PB potentially influences high-altitude sleep.
To test this hypothesis we performed nocturnal measurements of PB and wakefulness of four trekkers during a 6-day ascent from 760 meters to 3540 meters. This prospective study was carried out by medically savvy volunteers in March 2012. Table
Trekker demographics.
Subject | Gender | Age | Height (m) | Weight (kg) | BMI (kg/m2) | Sleep past medical history | Medications on trek |
---|---|---|---|---|---|---|---|
1 | M | 56 | 1.75 | 74 | 24.2 | No | No |
2 | F | 40 | 1.6 | 56 | 21.9 | No | No |
3 | M | 31 | 1.9 | 82 | 22.7 | No | No |
4 | F | 26 | 1.65 | 57 | 20.9 | No | No |
Ascent profile.
No interventions, invasive measures, or medications were used during this trek. As such, Institutional Review Board (IRB) approval was not obtained.
An actigraph differentiates sleep from wakefulness based on wrist movement. Estimation of sleep by actigraphy is highly correlated with sleep estimation by polysomnography [
A recording pulse oximeter worn on the nondominant hand was used to measure SaO2 and heart rate (Nonin 3100 WristOx, Nonin Medical Inc., Plymouth, MN, USA). Study subjects were instructed to put on the pulse oximeter when they went to bed and to remove the pulse oximeter the next morning when they arose. Time in periodic breathing was determined manually from periodic desaturations in a crescendo-decrescendo pattern lasting at least 3 cycles [
Contribution of subjects to sleep study.
Subject | Total hours of raw sleep data | Total hours of sleep analyzed | Total hours of sleep excluded | Hours excluded owing to less than 200 minutes of pulse oximetry recording | Hours excluded after pulse ox ended but actigraph still on/last hour of the night | Total number of awakenings | Total hours of periodic breathing |
---|---|---|---|---|---|---|---|
1 (E) | 88 | 60 | 28 | 9 | 19 | 21 | 10.8 |
2 (K) | 91 | 73 | 18 | 8 | 10 | 11 | 2.4 |
3 (J) | 91 | 80 | 11 | 0 | 11 | 29 | 8.4 |
4 (S) | 88 | 72 | 16 | 6 | 10 | 14 | 1.7 |
TOTAL |
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Overall, 358-hour raw data were available for analysis. The raw hourly data were further amended to 285 hours of analyzable data using the following hierarchy of exclusions: (1) nights with less than 200 minutes of pulse oximetry recording as this fragment was not likely to represent an adequate sleep sample and thus may omit the potential variations in breathing that occur during the different sleep stages throughout the night, (2) hours excluded after pulse oximetry measurements ended but actigraph was still on, and (3) final hour of sleep or the final hour of night. This final criterion was adopted because the final hour of sleep naturally includes a terminal awakening which may have distinct physiological and adaptive causes in comparison to midsleep awakenings [
For the purpose of this study, we defined “low altitude” to be <2670 meters and “high altitude” to be ≥2670 meters. This altitude was reached on the 6th day of the trek. This was chosen as the cut-off level for multiple reasons. Most notably, consensus high altitude scoring systems recognize elevations above 2,500 meters as those where the pernicious physiologic effects of acute high altitude become increasingly common and severe [
Average O2 saturation and percent of night spent in periodic breathing.
Altitude (m) | Avg O2 saturation (%) | % night in PB |
---|---|---|
760 | 95.6 | 1.2 |
1100 | 95.5 | 3.1 |
1700 | 95.4 | 1.7 |
2300 | 93.3 | 3.5 |
2670 | 91.0 | 5.3 |
3200 | 88.4 | 10.1 |
3540 | 87.2 | 13.0 |
Data were collected from each of the 4 subjects for a total of 10 nights (4 nights at low altitude and 6 nights at high altitude). During each night, evaluation on PB events and awakenings was done on the hourly basis. Depending on the nature of the parameter, data were analyzed by night (e.g., percentage of the night spent in PB) or by hour (e.g., PB or awakening event). Repeated measures analyses using Generalized Estimating Equations (GEE) techniques were used to take into account the multiple hourly or nightly measurements from the same subject. Statistical analysis was performed using SAS version 9.3 (The SAS Institute, Cary, NC).
Among the six nights spent at high altitude, the percentage of the night spent in PB ranged from 0.7% (subject 2 on night 5) to 34.4% (subject 1 on night 10). When averaging across the six nights at high altitude, the four subjects spent 21.8%, 4.1%, 15.2%, and 2.9% of the night in PB, respectively. When averaging across all nights at high altitude, subjects spent an average of
An awakening was categorized as a PB-associated awakening if there was a PB event at any point during the one minute prior to the awakening. Actigraphy calculated a total of 50 behavioral awakenings for all four climbers over the course of 6 nights at high altitude. 15 out of 50 of these awakenings (30%, 95% CI: 18–45%) were associated with PB (Table
Relationships between awakenings and associated periodic breathing events.
Altitude (meters) | Awakening not associated with PB |
Awakening associated with periodic breathing |
Total | % night spent in PB |
---|---|---|---|---|
<2670 m | 21 (91.3) | 2 (8.7) | 23 | 2.4 |
≥2670 m | 35 (70.0) | 15 (30) | 50 | 10.5 |
Total | 56 | 17 | 73 | 7.6 |
Decreased sleep quality is a near-universal finding at high altitude. While a significant component of the disruption in sleep architecture at high altitude is due to an increased incidence of PB, the role of PB’s influence on behavioral awakenings is poorly defined. This study presents data to further our understanding of this relationship.
In this study, we use actigraphy to capture data on patients’ behavioral awakenings. In contrast, many prior studies use polysomnography instead. Polysomnography is the gold standard for sleep studies [
In our study, we recognize the aforementioned limitations of actigraphy. For this reason, our study was not powered to evaluate sleep architecture, sleep quality or to determine the absolute number of awakenings that occurred during sleep. Rather, we simply used actigraphy as a tool to determine and analyze only a proportion of the total awakenings (behavioral) that occurred at night.
Furthermore, the majority of polysomnography data on sleep at high altitudes measures arousals and the Arousal Index (AI), the amount of arousals per hour. We, however, measured discrete behavioral awakenings as determined by actigraphy. Although these two terms are often used interchangeably in the literature, this is technically imprecise. One definition asserts that an “arousal” indicates cortical and physiological events linked to respiratory pathology whereas an “awakening” also indicates a behavioral element [
We examined the potential relationship between PB and behavioral awakenings by reviewing the minute prior to each awakening for evidence of a PB event. At high altitude, the average percent of time spent in PB among the 4 subjects was 10.5% (95% CI 6.5–14.6%). Interestingly, out of the 50 measured awakenings at high altitude, 30% were associated with periodic breathing (95% CI: 18–45%;
As previously stated, the majority of research on this topic looks at the relationship between periodic breathing and arousals and not awakenings. Johnson et al. and Salvaggio et al. both showed that while the total number of arousals tends to increase with the incidence of PB events, a large proportion of PB events do not elicit arousals [
These mixed conclusions illustrate the inherent difficulty in understanding the interrelationships between PB, arousals, awakenings, and other sleep disturbances. Some have suggested that PB lowers the threshold to arousals or awakenings. Among others, Khoo et al. have reported [
Weil postulated that PB during acclimatization at high altitudes likely reflects an individual’s ventilatory response to hypoxia. As such, there is great variability in the individual response to altitude [
There are several other limitations to the findings of this study. As with many studies on sleep at high altitude, we had a very small sample size. This limited the power of our study and made our results vulnerable to the effect of potential outliers. In the present study, two of the subjects contributed 83% of the time spent in periodic breathing. In order to adequately analyze the data obtained from a small group of subjects and compensate for individual variation, we studied each hour of sleep and each awakening as an isolated event. With a large number of hours and discrete events to study we were able to describe statistically significant findings which contribute to the growing body of research on this matter. Nonetheless, further study should be performed with larger sample sizes. Since this study was conducted at a moderately high altitude and gradual ascent rate, our findings cannot be generalized to scenarios or varying ascent rates and commonly mountaineered higher altitudes such as Mt. Kilimanjaro, the Andes, and Mt. Everest. Lastly, pharmacologic sleep aids such as Temazepam or Acetazolamide are commonly used during high altitude ascent. No such medications were used by the participants in this study, and, thus, it does not shed light on the relationship between PB and awakenings when these medications are used.
In the future, we believe it would be beneficial to further examine the potential mechanisms behind why PB may lead to a more wakeful state. Additionally, since much of the data are conflicting and all studies take place in unique settings, including different ascent rates and peak altitudes, varying weather conditions, and the use of pharmacologic sleep aids, we believe that a more controlled study (where a greater sample size would likely be more readily available) may help obviate any apparent inconsistences in the observed results and conclusions reached.
In conclusion, our data reveal a higher than expected number of awakenings that are associated with a PB. This finding suggests that PB plays a role in awakenings at high altitude.
This was not an industry supported study. There was no investigational or off label use. Institution in which work was performed was Division of Wilderness Medicine, Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA.
The authors have declared that there was no conflict of interests.
The authors would like to thank the Himalayan Rescue Association for providing logistical support. They would also like to thank Stephen R. Muza, Ph.D. holder, and the United States Army Research Institute of Environmental Medicine for providing the actigraphs and pulse oximeters.