Acute Altitude Acclimatization in Young Healthy Volunteers: Nocturnal Oxygenation Increases Over Time, Whereas Periodic Breathing Persists

Abstract

Ju, Jia-Der, Cristian Zhang, Francis P. Sgambati, Lidia M. Lopez, Luu V. Pham, Alan R. Schwartz, and Roberto A. Accinelli. Acute altitude acclimatization in young healthy volunteers: nocturnal oxygenation increases over time whereas periodic breathing persists. High Alt Med Biol. 22:14-23, 2021. Study Objectives: This study aimed to examine the acute effects of high altitude (HA) on sleep disordered breathing (sleep apnea and nocturnal hypoxemia) and acute mountain sickness and to characterize acclimatization over time. Methods: Ten native lowlanders residing at sea level (SL) completed the Lake Louise Score (LLS) and underwent nocturnal polygraphy (ApneaLink Plus) for nine consecutive nights (N1-N9) at HA (2,761 m) and two nights before and after HA. Nocturnal oxygen profiles were assessed by measuring the mean nocturnal oxyhemoglobin saturation (S_pO₂) during sleep, and sleep apnea severity as assessed by measuring the Apnea-Hypopnea Index (AHI). Mixed-effects linear regression was used to model responses in outcomes (mean nocturnal S_pO₂, logAHI, and LLS) between HA and SL. Changes in S_pO₂ and AHI were examined in subgroups with mild versus marked nocturnal S_pO₂ and low versus high AHI during exposure to HA and compared between subgroups. Results: Compared with SL, the mean nocturnal S_pO₂ was lower (p < 0.0001) and AHI was higher (p < 0.0001) at HA. The mean nocturnal S_pO₂ increased progressively (p < 0.001), whereas AHI remained high (p < 0.978) and relatively unchanged over nine successive nights at HA. Those with markedly reduced S_pO₂ upon arrival at HA exhibited progressive increases in the mean nocturnal S_pO₂ over time at HA compared with those with mild nocturnal desaturation. LLS rose at HA, but no differences were observed between subgroups. Conclusions: In healthy HA sojourners, the mean nocturnal S_pO₂ increased progressively over time, whereas AHI remained elevated, suggesting distinctive phenotypes and acclimatization responses to HA.

Keywords: high altitude; sleep; sleep disordered breathing.

FIG. 2.

Mean nocturnal S_pO₂ over the study time course. In each panel, the mean nocturnal S_pO₂ versus study night before, during, and after high altitude exposure for the entire group (all subjects, left panel) and for subgroups of marked (middle panel) and mild desaturators (right panel), based on median split of the mean nocturnal S_pO₂ values during the first two nights at HA. Night 8 was not considered for the analysis because subjects slept at a higher altitude during that night (from 2,750 to 2,970 m). *, Mean nocturnal S_pO₂ sea level versus high altitude; δ, mean nocturnal S_pO₂, first versus last night at HA. See results section, “Effect of altitude and acclimatization on nocturnal oxyhemoglobin saturation profile.” S_pO₂, oxyhemoglobin saturation.

FIG. 1.

Illustrative nocturnal oxygen profiles at high altitude. S_pO₂ versus time (hours) for illustrative nocturnal sleep recordings during the first night at HA. Top panel (A) illustrates the trace of a representative subject with intermittent hypoxemia with relatively high mean S_pO₂. Middle and bottom panels (B, C) exhibit different nocturnal S_pO₂ tracings of representative subjects from subgroups with marked and mild reductions in mean S_pO₂ and no significant sleep apnea, respectively. Red line shows the mean nocturnal S_pO₂ during the night. AHI values are reported for each tracing. AHI, Apnea–Hypopnea Index; HA, high altitude; S_pO₂, oxyhemoglobin saturation.

FIG. 3.

AHI over the study time course. In each panel, AHI versus study night before, during, and after high altitude exposure for the entire group (all subjects, left panel) and for subgroups of marked (middle panel) and mild desaturators (right panel), based on median split of AHI values during the first two nights at HA. *, AHI sea level versus AHI high altitude; δ, AHI high altitude first night (HA first) versus high altitude last night (HA last); μ, AHI high altitude deep desaturators versus high altitude mild desaturators. See results section, “Effect of altitude and acclimatization on sleep apnea.”

FIG. 4.

Differences in the mean nocturnal S_pO₂ in AHI subgroups. In each panel, the mean nocturnal S_pO₂ versus study night before, during and after high altitude exposure for the subgroups of low AHI (left panel) and high AHI (right panel), based on median split of AHI values during the first two nights at HA. *, AHI high altitude first night (HA first) versus high altitude last night (HA last); δ, high altitude versus low altitude. See results section, “Effect of altitude and acclimatization on sleep apnea.” S_pO₂, oxyhemoglobin saturation.

FIG. 5.

Nocturnal ventilatory phenotypes during sleep at high altitude. Diagram illustrates the mechanism by which nocturnal ventilatory phenotypes during sleep at HA develop. Sleep can be considered a physiological stress for the respiratory system, which aggravates with altitude hypobaric hypoxia. This increased burden during sleep at HA can trigger compensatory mechanisms for the maintenance of nocturnal S_pO₂. All subjects experience nocturnal hypoxemia during sleep, but some experience sharp decreases in the mean nocturnal S_pO₂ with few central apneas (if they have a high arousal threshold), whereas others will maintain the mean nocturnal S_pO₂ but demonstrate high frequencies of central apneas (low arousal threshold). These two phenotypes are characterized by either sleep continuity at expense of hypoventilation and desaturation, or frequent arousals from nocturnal alterations in gas exchange, thereby maintaining ventilation and oxygenation at expense of sleep continuity.