Partial Pressure of Arterial Oxygen in Healthy Adults at High Altitudes: A Systematic Review and Meta-Analysis.

Importance: With increasing altitude, the partial pressure of inspired oxygen decreases and, consequently, the Pao2 decreases. Even though this phenomenon is well known, the extent of the reduction as a function of altitude remains unknown. Objective: To calculate an effect size estimate for the decrease in Pao2 with each kilometer of vertical gain among healthy unacclimatized adults and to identify factors associated with Pao2 at high altitude (HA). Data Sources: A systematic search of PubMed and Embase was performed from database inception to April 11, 2023. Search terms included arterial blood gases and altitude. Study Selection: A total of 53 peer-reviewed prospective studies in healthy adults providing results of arterial blood gas analysis at low altitude (<1500 m) and within the first 3 days at the target altitude (≥1500 m) were analyzed. Data Extraction and Synthesis: Primary and secondary outcomes as well as study characteristics were extracted from the included studies, and individual participant data (IPD) were requested. Estimates were pooled using a random-effects DerSimonian-Laird model for the meta-analysis. Main Outcomes and Measures: Mean effect size estimates and 95% CIs for reduction in Pao2 at HA and factors associated with Pao2 at HA in healthy adults. Results: All of the 53 studies involving 777 adults (mean [SD] age, 36.2 [10.5] years; 510 men [65.6%]) reporting 115 group ascents to altitudes between 1524 m and 8730 m were included in the aggregated data analysis; 13 of those studies involving 305 individuals (mean [SD] age, 39.8 [13.6] years; 185 men [60.7%]) reporting 29 ascents were included in the IPD analysis. The estimated effect size of Pao2 was -1.60 kPa (95% CI, -1.73 to -1.47 kPa) for each 1000 m of altitude gain (τ2 = 0.14; I2 = 86%). The Pao2 estimation model based on IPD data revealed that target altitude (-1.53 kPa per 1000 m; 95% CI, -1.63 to -1.42 kPa per 1000 m), age (-0.01 kPa per year; 95% CI, -0.02 to -0.003 kPa per year), and time spent at an altitude of 1500 m or higher (0.16 kPa per day; 95% CI, 0.11-0.21 kPa per day) were significantly associated with Pao2. Conclusions and Relevance: In this systematic review and meta-analysis, the mean decrease in Pao2 was 1.60 kPa per 1000 m of vertical ascent. This effect size estimate may improve the understanding of physiological mechanisms, assist in the clinical interpretation of acute altitude illness in healthy individuals, and serve as a reference for physicians counseling patients with cardiorespiratory disease who are traveling to HA regions.

Anti-IgLON5 Disease: A New Bulbar-Onset Motor Neuron Mimic Syndrome.

OBJECTIVE: To expand the spectrum of anti-IgLON5 disease by adding 5 novel anti-IgLON5-seropositive cases with bulbar motor neuron disease-like phenotype. METHODS: We characterized the clinical course, brain MRI and laboratory findings, and therapy response in these 5 patients. RESULTS: Patients were severely affected by bulbar impairment and its respiratory consequences. Sleep-related breathing disorders and parasomnias were common. All patients showed clinical or electrophysiologic signs of motor neuron disease without fulfilling the diagnostic criteria for amyotrophic lateral sclerosis. One patient regained autonomy in swallowing and eating, possibly related to immunotherapy. CONCLUSION: IgLON5 disease is an important differential diagnosis to evaluate in patients with bulbar motor neuron disease-like phenotype and sleep disorders. There is need for a deeper understanding of the underlying pathobiology to determine whether IgLON5 disease is an immunotherapy-responsive condition.

Actigraphy of Wrist and Ankle for Measuring Sleep Duration in Altitude Travelers.

Latshang, Tsogyal Daniela, Daniela Juliana Mueller, Christian Maurizio Lo Cascio, Anne-Christin Stöwhas, Katrin Stadelmann, Noemi Tesler, Peter Achermann, Reto Huber, Malcolm Kohler, and Konrad Ernst Bloch. Actigraphy of wrist and ankle for measuring sleep duration in altitude travelers. High Alt Med Biol. 17:194-202, 2016-Aims: Actigraphy might be convenient to assess sleep disturbances in altitude field studies. Therefore, we evaluated whether actigraphy accurately measures sleep duration in healthy subjects traveling to altitude. METHODS: Fifty-one healthy men, aged mean ± standard deviation (SD) 27 ± 9 years, were studied during one night at Zurich (490 m), two nights at Davos Wolfgang (1630 m), and two nights at Jakobshorn (2590 m), in randomized order. Sleep duration measured by actigraphy, using a one-axis device at the wrist (n = 51), a three-axis device at the other wrist, and a three-axis device at the ankle (n = 22), was compared with corresponding total sleep time (TST) measured by polysomnography. RESULTS: During 255 polysomnographic overnight studies, 449 paired actigraphic recordings were obtained. The median polysomnographic-derived TST ranged from 397 to 408 minutes. Actigraphic mean TST from wrists with one-axis and three-axis devices, and from ankle agreed well with polysomnographic values with a bias of +1, -7, +6 minutes, respectively. Corresponding limits of agreement (±2 SD of bias) were ±51, ±60, and ±59 minutes. Limits of agreement of mean TST over five nights by actigraphy and polysomnography were similar to the coefficient of repeatability (2 SD of mean) of polysomnographic TST, that is, ±31, ±38, and ±36 minutes versus ±34 minutes. CONCLUSIONS: Actigraphy of the wrist or ankle by a one-axis or a three-axis device accurately estimates mean TST in groups of subjects and mean TST over several nights in individuals traveling to altitude. Therefore, actigraphy is valuable for assessing effects of altitude and other environmental influences on sleep duration during field studies over extended periods.

Patients with Obstructive Sleep Apnea Have Cardiac Repolarization Disturbances when Travelling to Altitude: Randomized, Placebo-Controlled Trial of Acetazolamide.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) promotes myocardial electrical instability and may predispose to nocturnal sudden cardiac death. We evaluated whether hypobaric hypoxia during altitude travel further impairs cardiac repolarization in patients with OSA, and whether this is prevented by acetazolamide, a drug known to improve oxygenation and central sleep apnea at altitude. METHODS: Thirty-nine OSA patients living < 600 m, discontinued continuous positive airway pressure therapy during studies at 490 m and during two sojourns of 3 days at altitude (2 days at 1860 m, 1 day at 2590 m). During one altitude sojourn, patients took acetazolamide, during the other placebo, or vice versa, according to a randomized, double-blind crossover design. Twelve-lead electrocardiography and pulse oximetry (SpO2) were recorded during nocturnal polysomnography. Heart rate corrected mean QT intervals during the entire night (meanQTc) and during 1 min of the night with the longest meanQTc (maxQTc) were determined. RESULTS: At 490 m the median nocturnal SpO2 was 93%, medians of meanQTc and maxQTc were 420 ms and 478 ms. At 2590 m, on placebo, SpO2 was lower (85%), and meanQTc and maxQTc were prolonged to 430 ms and 510 ms (P < 0.02 vs. 490 m, all corresponding comparisons). At 2590 m on acetazolamide, median SpO2 was increased to 88% (P < 0.05 vs. placebo), meanQTc was reduced to 427 ms (P < 0.05 vs. placebo), whereas maxQTc remained increased at 502 ms (P = ns vs. placebo). CONCLUSIONS: At 2590 m OSA patients experienced cardiac repolarization disturbances in association with hypoxemia. Prolongation of meanQTc at altitude was prevented and hypoxemia was improved by acetazolamide, whereas maxQTc remained increased suggesting imperfect protection from repolarization disturbances. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NTC-00714740. URL: www.clinicaltrials.gov.