**1. Introduction**

Every year, thousands of people come from the lowlands to high altitude such as the Qinghai-Tibetan plateau, the Andes, and the Alps, for sight-seeing and mountaineering. Although identification on high altitude is controversial [1, 2] (see **Table 1**), altitude illnesses do not generally occur until 2500 m altitude or greater [2]. Currently, there are hundreds of thousands of non-native people working and living in these areas at altitudes ranging from 4000 to 5072 m including mountaineers, search and rescue personnel, and military personnel.

Poor sleep quality is a common experience for new arrivals at high altitude in the days to weeks following acute ascent. They often encounter with increased awakenings, frequent brief arousals, a sense of suffocation relieved by a few deep breaths, and resumption of sleep, which is now known as periodic breathing (PB). Upon arising from sleep, the impression is one of greatly restless sleep. Poor sleep quality at high altitude is one of the serious complaints in people with mountain sickness and influences physical and mental well-being, which can manifest as impaired cognitive abilities [3, 4] and poor daytime performance [5]. Up to now,


**Table 1.**

*Identification of high altitude.*

there are no acceptable diagnostic criteria for sleep disorder at high altitude. It is recognized as a symptom of mountain sickness rather than an altitude disease.

Here we discuss the features of sleep at high altitude with focus on the role and causes of PB in altitude sleep disturbance, subjective changes in sleep quality, objective variations in sleep architecture, and management of sleep disorder at high altitude. We also discuss whether it is appropriate to name it high-altitude sleep disorder (HASD) as one of the altitude-related illness in accordance with the nomenclature of other high-altitude diseases.

> from ensuing hypocapnia. These changes lead to alterations in chemoreflex control and cerebrovascular responses to changes in arterial O2 which finally result in hyperventilation. For lowlanders, acclimatization to high altitude magnifies these changes. Briefly, an elevated chemosensitivity causes a more vigorous response to the rise in PaCO2 while the apnea outweighs the improvements in the effectiveness of ventilation in changing the arterial O2 caused by the chronic hypocapnia leading

*Periodic breathing during sleep between native Tibetans and acclimatized Han lowlanders at 3800 altitude.*

The severity of PB is determined to be aggravated by an increasing neural respiratory drive (NRD), which can be measured by the electromyogram of the diaphragm. A sleep study in four healthy mountaineers performed at 3380, 4370, and 5570 m in the Andes, Argentina, confirmed this hypothesis [15]. A high NRD at altitude leads to a higher ventilation to maintain oxygenation, which results in more significant hypocapnia. This triggers apneas and O2 desaturations, as indicated by the positive correlation between the EMG of the diaphragm and the O2 desaturation index. PB is considered to contribute to and/or be a result of sleep fragmentation by frequent arousals which may be responsible for poor sleep quality following altitude

Therefore, the uncomfortable sensation of sleep at high altitude is largely due to respiratory disturbance arising from the physiologic ventilatory dilemma of acute ascent, where stimulation by hypoxia alternates with inhibition by hypocapnic

Subjective sleep quality at high altitude is usually evaluated by a questionnaire, e.g., sleep log questions, Pittsburgh Sleep Quality Index (PSQI), and Athens Insomnia Score (AIS). The prevalence of sleep disorder may differ considerably at altitude

ascent. Sleep and arousals lead to greater breathing instability. Apnea is in correspondence to an increase in PaCO2 and decrease in PaO2 and consequently unstable ventilation. These changes in blood gases also lead to marked alterations in cerebral blood flow (CBF) which, in turn, may result in a sudden elevation (with

reduced CBF) or reduction (with increased CBF) in brain stem pH.

**3.1 Evaluation and prevalence of poor sleep quality at high altitude**

**3. Poor subjective sleep quality at high altitude**

to the occurrence of PB [14].

*Modified from Kong et al. [12].*

*Sleep Disorder at High Altitude*

*DOI: http://dx.doi.org/10.5772/intechopen.86727*

**Figure 1.**

alkalosis.

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#### **2. Breathing disturbance during sleep at high altitude**

One of the most important characteristics of sleep disorder at high altitude is PB, which usually occurs at altitudes above 2000 m [6]. PB during sleep was first recorded in 1886 by Mosso [7] and further observed by Douglas and Haldane in 1909 [8]. It is considered that under high altitude hypoxic circumstances, breathing was stimulated by hypoxia, leading to hypocapnia and lessening of hypoxia, which triggers apnea during sleep. Apnea, in turn, restores ventilatory by raising PCO2 and increasing hypoxia, generating the periodic respiratory cycle. This cyclical crescendo-decrescendo pattern periodicity usually consists of 2–4 breaths, separated by an apnea of 5–15 s in duration from the next burst of 2–4 breaths. Therefore, unstable breathing is the main characteristic of PB.

The extent of PB increased progressively as the altitude increased [9]. There is a strong positive correlation between PB and severity of acute mountain sickness (AMS) as assessed by Lake Louise (LL) score. With the increasing of altitude, normal values for partial pressure of arterial (PaO2) decreased compared to sea level, pH changing to respiratory alkalosis with concomitant hypocapnia [10]. Above 4000 m altitude, PB exists in most people, but this phenomenon may be beneficial, because with the worsening of PB, a higher arterial oxygen saturation (SaO2) was observed during sleep [10, 11]. After 3 months of acclimatization at 3800 altitude, PB could also be observed in lowlanders. Although acclimatized lowlanders experienced PB more frequently than native Tibetans at 89–85% of SaO2 stage, there is no significant difference in total PB events occurring either in nonrapid eye movement (NREM) or rapid eye movement (REM) stage [12]. See details in **Figure 1**, periodic breathing during sleep between native Tibetans and acclimatized Han lowlanders at 3800 m altitude. Even for a longer time (13 months) of camp in the Antarctic base Concordia (3800 m), PB prevailed for the major part of sleeping time [13]. These findings from a cross-sectional and a longitudinal study support our current understanding which assumes PB would not be largely relieved after acclimatization.

The mechanism underlying this respiratory pattern for apnea and PB during sleep in hypoxic environments is believed to be a reduction in the PaO2 and acidbase adjustments. The procedure of PB may be summarized as conflicting dynamics between hypoxic stimulation of ventilation and suppression of respiratory output

**Figure 1.**

there are no acceptable diagnostic criteria for sleep disorder at high altitude. It is recognized as a symptom of mountain sickness rather than an altitude disease.

High altitude Beyond 2400 m 2500 m–3500 m Very high altitude Beyond 4000 m 3500 m–5800 m Extremely high altitude Beyond 5500 m Beyond 5800 m

causes of PB in altitude sleep disturbance, subjective changes in sleep quality, objective variations in sleep architecture, and management of sleep disorder at high altitude. We also discuss whether it is appropriate to name it high-altitude sleep disorder (HASD) as one of the altitude-related illness in accordance with the

nomenclature of other high-altitude diseases.

*Updates in Sleep Neurology and Obstructive Sleep Apnea*

**Table 1.**

*Identification of high altitude.*

**2. Breathing disturbance during sleep at high altitude**

fore, unstable breathing is the main characteristic of PB.

after acclimatization.

**110**

Here we discuss the features of sleep at high altitude with focus on the role and

**Davis et al. [1] Rolan [2]**

One of the most important characteristics of sleep disorder at high altitude is PB,

The extent of PB increased progressively as the altitude increased [9]. There is a strong positive correlation between PB and severity of acute mountain sickness (AMS) as assessed by Lake Louise (LL) score. With the increasing of altitude, normal values for partial pressure of arterial (PaO2) decreased compared to sea level, pH changing to respiratory alkalosis with concomitant hypocapnia [10]. Above 4000 m altitude, PB exists in most people, but this phenomenon may be beneficial, because with the worsening of PB, a higher arterial oxygen saturation (SaO2) was observed during sleep [10, 11]. After 3 months of acclimatization at 3800 altitude, PB could also be observed in lowlanders. Although acclimatized lowlanders experienced PB more frequently than native Tibetans at 89–85% of SaO2 stage, there is no significant difference in total PB events occurring either in nonrapid eye movement (NREM) or rapid eye movement (REM) stage [12]. See details in **Figure 1**, periodic breathing during sleep between native Tibetans and acclimatized Han lowlanders at 3800 m altitude. Even for a longer time (13 months) of camp in the Antarctic base Concordia (3800 m), PB prevailed for the major part of sleeping time [13]. These findings from a cross-sectional and a longitudinal study support our current understanding which assumes PB would not be largely relieved

The mechanism underlying this respiratory pattern for apnea and PB during sleep in hypoxic environments is believed to be a reduction in the PaO2 and acidbase adjustments. The procedure of PB may be summarized as conflicting dynamics between hypoxic stimulation of ventilation and suppression of respiratory output

which usually occurs at altitudes above 2000 m [6]. PB during sleep was first recorded in 1886 by Mosso [7] and further observed by Douglas and Haldane in 1909 [8]. It is considered that under high altitude hypoxic circumstances, breathing was stimulated by hypoxia, leading to hypocapnia and lessening of hypoxia, which triggers apnea during sleep. Apnea, in turn, restores ventilatory by raising PCO2 and

increasing hypoxia, generating the periodic respiratory cycle. This cyclical crescendo-decrescendo pattern periodicity usually consists of 2–4 breaths, separated by an apnea of 5–15 s in duration from the next burst of 2–4 breaths. There-

*Periodic breathing during sleep between native Tibetans and acclimatized Han lowlanders at 3800 altitude. Modified from Kong et al. [12].*

from ensuing hypocapnia. These changes lead to alterations in chemoreflex control and cerebrovascular responses to changes in arterial O2 which finally result in hyperventilation. For lowlanders, acclimatization to high altitude magnifies these changes. Briefly, an elevated chemosensitivity causes a more vigorous response to the rise in PaCO2 while the apnea outweighs the improvements in the effectiveness of ventilation in changing the arterial O2 caused by the chronic hypocapnia leading to the occurrence of PB [14].

The severity of PB is determined to be aggravated by an increasing neural respiratory drive (NRD), which can be measured by the electromyogram of the diaphragm. A sleep study in four healthy mountaineers performed at 3380, 4370, and 5570 m in the Andes, Argentina, confirmed this hypothesis [15]. A high NRD at altitude leads to a higher ventilation to maintain oxygenation, which results in more significant hypocapnia. This triggers apneas and O2 desaturations, as indicated by the positive correlation between the EMG of the diaphragm and the O2 desaturation index.

PB is considered to contribute to and/or be a result of sleep fragmentation by frequent arousals which may be responsible for poor sleep quality following altitude ascent. Sleep and arousals lead to greater breathing instability. Apnea is in correspondence to an increase in PaCO2 and decrease in PaO2 and consequently unstable ventilation. These changes in blood gases also lead to marked alterations in cerebral blood flow (CBF) which, in turn, may result in a sudden elevation (with reduced CBF) or reduction (with increased CBF) in brain stem pH.

Therefore, the uncomfortable sensation of sleep at high altitude is largely due to respiratory disturbance arising from the physiologic ventilatory dilemma of acute ascent, where stimulation by hypoxia alternates with inhibition by hypocapnic alkalosis.

### **3. Poor subjective sleep quality at high altitude**

#### **3.1 Evaluation and prevalence of poor sleep quality at high altitude**

Subjective sleep quality at high altitude is usually evaluated by a questionnaire, e.g., sleep log questions, Pittsburgh Sleep Quality Index (PSQI), and Athens Insomnia Score (AIS). The prevalence of sleep disorder may differ considerably at altitude from observational studies. At a 3500 m hotel, 46% of 100 Iranian ski tourists reported frequent awakenings and other subjective sleep disturbances [16]. At an altitude of 3700 m in Lhasa, Tibet, 36.8% of 180 Chinese stationed soldiers reported poor sleep quality as measured by PSQI [17]. Data analysis from the same sample also indicated that poor sleepers (defined as PSQI > 5) were 1.45 times greater in those with polycythemia than those without polycythemia [95% (confidence interval) CI 1.82–2.56] [4]. Report from early pharmacologic treatment trials in acute mountain sickness (AMS) suggested that 53–71% of participants reported difficulty sleeping [18, 19]. Of note, despite the 3 months of acclimatization, a greater proportion of poor sleepers were still observed in lowlanders stationed at 3800 altitude than the native Tibetans (90.91 vs. 45.45%, P = 0.004) [12].

For people with CMS stationed at Tibet, the proportion of poor sleepers (defined as PSQI > 5) with severe CMS was 12.54-fold higher than that of good sleepers. See **Figure 2**, CMS severity comparison between "good" and "poor" sleepers at 3996 m altitude. Subjects with CMS had higher scores in each sleep component of the PSQI score, except the use of sleep medication. After adjusted for CMS score, age, and education, poor sleep quality was determined to be an independent predictor of impaired intelligence quotient [odds ratio (OR) 1.59, 95% CI 1.30–1.95] and short-term memory (OR 1.18, 95% CI 1.07–1.31).

Therefore, for people with CMS, the poorer the sleep quality, the worse was the

Polysomnography (PSG) is the gold standard for investigating sleep architecture. However, the technical complexity and logistic demands had brought restriction on its utilization during altitude studies. Although there are several studies that suggest wrist actigraphy-derived data on total sleep time, sleep efficiency and sleep

Objective assessment of sleep architecture at altitude by electroencephalogram was first reported by Joern et al. in 1970 [25]. They found a near absence of stages 3 and 4 and a 50% reduction in rapid eye movement (REM) sleep and reported PB and arousals in one subject. A later study in 1975 confirmed a decrease in deeper sleep and increase in lighter sleep stages and brief arousals after ascending to an altitude of 4300 m at the Pikes Peak when compared to subjects at low altitude [26]. Subsequent studies have generally confirmed the shift at altitude toward lighter sleep stages, with a variable change in duration of REM sleep and increased awak-

Alterations in objective sleep parameters have also been observed during acclimatization. A recent literature review on high-altitude sleep concludes that during rapid ascent to high altitude, there is a reduction in total sleep time, sleep efficiency, and deep sleep (stages 3 and 4) (in new nomenclature N3) and a significant increase in arousals and PB [31]. These variations are possibly high altitude dependent, and the effects tend to moderate with acclimatization [6]. Hypnograms of a partially acclimatized lowlander sleeping and a native Tibetan sleeping at high altitude are

Although subjective sleep quality is impaired at high altitude, attempts to find a correlation between objective and subjective measures have failed to find a connection [24]. One study investigated 63 participants who completed a 3-hour flight from sea level to the South Pole (3200 m) and discovered no association between self-reported sleep quality and sleep efficiency, nocturnal oxygen saturation, and apnea/hypopnea index (AHI) obtained from PSG [32]. When assessed by LL score, there was no significant correlation of the subjective sleep measurement compared to sleep efficiency derived from PSG and actigraphy [24]. Another study investigated 165 young male soldiers stationed in Tibet Plateau (3800 m) for at least 3 months. In a multiple regression model adjusted for age, service time, body mass index, Epworth Sleepiness Scale, anxiety, and depression, sleep onset latency (b = 0.08, 95% CI: 0.01–0.15) and NREM latency (b = 0.011, 95% CI: 0.001–0.02) obtained from PSG were slightly positively correlated with global PSQI, while mean nocturnal SpO2 (b = 0.79, 95% CI: 1.35 to 0.23) and time in stage 3 + 4 sleep (b = 0.014, 95% CI: 0.001 to 0.028) was slightly negatively associated with

onset latency were similar to those of PSG [24]; actigraphy is insufficient in

**4. Variation of sleep architecture at high altitude**

detecting sleep stage and breathing events.

enings associated with PB [27–30].

shown in **Figures 3** and **4**.

global PSQI [12].

**113**

cognitive function [4].

*Sleep Disorder at High Altitude*

*DOI: http://dx.doi.org/10.5772/intechopen.86727*

#### **3.2 Sleep quality and severity of mountain sickness**

Poor sleep quality at high altitude was one of the most frequently reported symptoms in mountain sickness as assessed by the Lake Louise Symptom Questionnaire and the Qinghai Chronis Mountain Score [12], which are used to diagnose AMS [20] and evaluate severity of chronic mountain sickness(CMS) [21], respectively. This was confirmed by a study using PSQI and AIS which reports decreased subjective sleep quality at high altitude, especially reduced general sleep quality and prolonged sleep induction [22]. For workers rapidly transported from sea level to high altitude, there are no statistically significant differences in polysomnographic parameters between subjects with AMS and those without AMS [23].

#### *Sleep Disorder at High Altitude DOI: http://dx.doi.org/10.5772/intechopen.86727*

from observational studies. At a 3500 m hotel, 46% of 100 Iranian ski tourists reported frequent awakenings and other subjective sleep disturbances [16]. At an altitude of 3700 m in Lhasa, Tibet, 36.8% of 180 Chinese stationed soldiers reported poor sleep quality as measured by PSQI [17]. Data analysis from the same sample also indicated that poor sleepers (defined as PSQI > 5) were 1.45 times greater in those with polycythemia than those without polycythemia [95% (confidence interval) CI 1.82–2.56] [4]. Report from early pharmacologic treatment trials in acute mountain sickness (AMS) suggested that 53–71% of participants reported difficulty sleeping [18, 19]. Of note, despite the 3 months of acclimatization, a greater proportion of poor sleepers were still observed in lowlanders stationed at 3800 altitude

Poor sleep quality at high altitude was one of the most frequently reported symptoms in mountain sickness as assessed by the Lake Louise Symptom Questionnaire and the Qinghai Chronis Mountain Score [12], which are used to diagnose AMS [20] and evaluate severity of chronic mountain sickness(CMS) [21], respectively. This was confirmed by a study using PSQI and AIS which reports decreased subjective sleep quality at high altitude, especially reduced general sleep quality and prolonged sleep induction [22]. For workers rapidly transported from sea level to high altitude, there are no statistically significant differences in polysomnographic

parameters between subjects with AMS and those without AMS [23].

*Sleep quality comparison among different CMS severity at 3996 altitude. Modified from Kong et al. [4].*

than the native Tibetans (90.91 vs. 45.45%, P = 0.004) [12].

**3.2 Sleep quality and severity of mountain sickness**

*Updates in Sleep Neurology and Obstructive Sleep Apnea*

**Figure 2.**

**112**

For people with CMS stationed at Tibet, the proportion of poor sleepers (defined as PSQI > 5) with severe CMS was 12.54-fold higher than that of good sleepers. See **Figure 2**, CMS severity comparison between "good" and "poor" sleepers at 3996 m altitude. Subjects with CMS had higher scores in each sleep component of the PSQI score, except the use of sleep medication. After adjusted for CMS score, age, and education, poor sleep quality was determined to be an independent predictor of impaired intelligence quotient [odds ratio (OR) 1.59, 95% CI 1.30–1.95] and short-term memory (OR 1.18, 95% CI 1.07–1.31). Therefore, for people with CMS, the poorer the sleep quality, the worse was the cognitive function [4].
