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At altitude, factors such as decreased barometric pressure, low temperatures, and acclimatization might affect lung function. The effects of exposure and acclimatization to high-altitude on lung function were assessed in 39 subjects by repetitive spirometry up to 6022 m during a high-altitude expedition. Subjects were classified depending on the occurrence of acute mountain sickness (AMS) and summit success to evaluate whether lung function relates to successful climb and risk of developing AMS. Peak expiratory flow (PEF), forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) increased with progressive altitude (max. +20.2 %pred, +9.3 %pred, and +6.7 %pred, all p<0.05). Only PEF improved with acclimatization (BC1 vs. BC2, +7.2 %pred, p=0.044). At altitude FEV1 (p=0.008) and PEF (p<0.001) were lower in the AMS group. The risk of developing AMS was associated with lower baseline PEF (p<0.001) and longitudinal changes in PEF (p=0.008) and FEV1 (p<0.001). Lung function was not related to summit success (7126 m). Improvement in PEF after acclimatization might indicate respiratory muscle adaptation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: High altitude regions are characterized by harsh conditions (environmental, rough terrain, natural hazards, and limited hygiene and health care), which all may contribute to the risk of accidents/emergencies when trekking or climbing. Exposure to hypoxia, cold, wind, and solar radiation are typical features of the high altitude environment. Emergencies in these remote areas place high demands on the diagnostic and treatment skills of doctors and first-aiders. The aim of this review is to give insights on providing the best possible care for victims of emergencies at high altitude. Methods: Authors provide clinical recommendations based on their real-world experience, complemented by appropriate recent studies and internationally reputable guidelines. Results and Discussion: This review covers most of the emergencies/health issues that can occur when trekking or during high altitude climbing, that is, high altitude illnesses and hypothermia, freezing cold injuries, accidents, for example, with severe injuries due to falling, cardiovascular and respiratory illnesses, abdominal, musculoskeletal, eye, dental, and skin issues. We give a summary of current recommendations for emergency care and pain relief in case of these various incidents.

Objective: During a high-altitude expedition, the association of cardiopulmonary exercise testing (CPET) parameters with the risk of developing acute mountain sickness (AMS) and the chance of reaching the summit were investigated., Methods: Thirty-nine subjects underwent maximal CPET at lowlands and during ascent to Mount Himlung Himal (7126 m) at 4844 m, before and after 12 days of acclimatisation, and at 6022 m. Daily records of Lake-Louise-Score (LLS) determined AMS. Participants were categorised as AMS+ if moderate to severe AMS occurred., Results: Maximal oxygen uptake (V̇O 2max ) decreased by 40.5%±13.7% at 6022 m and improved after acclimatisation (all p<0.001). Ventilation at maximal exercise (VE max ) was reduced at 6022 m, but higher VE max was related to summit success (p=0.031). In the 23 AMS+ subjects (mean LLS 7.4±2.4), a pronounced exercise-induced oxygen desaturation (ΔSpO 2exercise ) was found after arrival at 4844 m (p=0.005). ΔSpO 2exercise >-14.0% identified 74% of participants correctly with a sensitivity of 70% and specificity of 81% for predicting moderate to severe AMS. All 15 summiteers showed higher V̇O 2max (p<0.001), and a higher risk of AMS in non-summiteers was suggested but did not reach statistical significance (OR: 3.64 (95% CI: 0.78 to 17.58), p=0.057). V̇O 2max ≥49.0 mL/min/kg at lowlands and ≥35.0 mL/min/kg at 4844 m predicted summit success with a sensitivity of 46.7% and 53.3%, and specificity of 83.3% and 91.3%, respectively., Conclusion: Summiteers were able to sustain higher VE max throughout the expedition. Baseline V̇O 2max below 49.0 mL/min/kg was associated with a high chance of 83.3% for summit failure, when climbing without supplemental oxygen. A pronounced drop of SpO 2exercise at 4844 m may identify climbers at higher risk of AMS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Areas at high-altitude, annually attract millions of tourists, skiers, trekkers, and climbers. If not adequately prepared and not considering certain ascent rules, a considerable proportion of those people will suffer from acute mountain sickness (AMS) or even from life-threatening high-altitude cerebral (HACE) or/and pulmonary edema (HAPE). Reduced inspired oxygen partial pressure with gain in altitude and consequently reduced oxygen availability is primarily responsible for getting sick in this setting. Appropriate acclimatization by slowly raising the hypoxic stimulus (e.g., slow ascent to high altitude) and/or repeated exposures to altitude or artificial, normobaric hypoxia will largely prevent those illnesses. Understanding physiological mechanisms of acclimatization and pathophysiological mechanisms of high-altitude diseases, knowledge of symptoms and signs, treatment and prevention strategies will largely contribute to the risk reduction and increased safety, success and enjoyment at high altitude. Thus, this review is intended to provide a sound basis for both physicians counseling high-altitude visitors and high-altitude visitors themselves., Competing Interests: The authors have no conflict of interest., (© 2021 The Authors.)

Key Points: A physiological response to increase microcirculatory oxygen extraction capacity at high altitude is to recruit capillaries. In the present study, we report that high altitude-induced sublingual capillary recruitment is an intrinsic mechanism of the sublingual microcirculation that is independent of changes in cardiac output, arterial blood pressure or systemic vascular hindrance. Using a topical nitroglycerin challenge to the sublingual microcirculation, we show that high altitude-related capillary recruitment is a functional response of the sublingual microcirculation as opposed to an anatomical response associated with angiogenesis. The concurrent presence of a low capillary density and high microvascular reactivity to topical nitroglycerin at sea level was found to be associated with a failure to reach the summit, whereas the presence of a high baseline capillary density with the ability to further increase maximum recruitable capillary density upon ascent to an extreme altitude was associated with summit success., Abstract: A high altitude (HA) stay is associated with an increase in sublingual capillary total vessel density (TVD), suggesting microvascular recruitment. We hypothesized that microvascular recruitment occurs independent of cardiac output changes, that it relies on haemodynamic changes within the microcirculation as opposed to structural changes and that microcirculatory function is related to individual performance at HA. In 41 healthy subjects, sublingual handheld vital microscopy and echocardiography were performed at sea level (SL), as well as at 6022 m (C2) and 7042 m (C3), during ascent to 7126 m within 21 days. Sublingual topical nitroglycerin was applied to measure microvascular reactivity and maximum recruitable TVD (TVD NG ). HA exposure decreased resting cardiac output, whereas TVD (mean ± SD) increased from 18.81 ± 3.92 to 20.92 ± 3.66 and 21.25 ± 2.27 mm mm -2 (P < 0.01). The difference between TVD and TVD NG was 2.28 ± 4.59 mm mm -2 at SL (P < 0.01) but remained undetectable at HA. Maximal TVD NG was observed at C3. Those who reached the summit (n = 15) demonstrated higher TVD at SL (P < 0.01), comparable to TVD NG in non-summiters (n = 21) at SL and in both groups at C2. Recruitment of sublingual capillary TVD to increase microcirculatory oxygen extraction capacity at HA was found to be an intrinsic mechanism of the microcirculation independent of cardiac output changes. Microvascular reactivity to topical nitroglycerin demonstrated that HA-related capillary recruitment is a functional response as opposed to a structural change. The performance of the vascular microcirculation needed to reach the summit was found to be associated with a higher TVD at SL and the ability to further increase TVD NG upon ascent to extreme altitude., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

Background: Assessment of the microcirculation is a promising target for the hemodynamic management of critically ill patients. However, just as the sole reliance on macrocirculatory parameters, single static parameters of the microcirculation may not represent a sufficient guide. Our hypothesis was that by serial topical application of acetylcholine (ACH) and nitroglycerin (NG), the sublingual microcirculation can be challenged to determine its endothelial cell-dependent and smooth muscle-dependent physiological reserve capacity., Methods: In 41 healthy subjects, sublingual capillary microscopy was performed before and after topical application of ACH and NG. Total vessel density (TVD) was assessed in parallel using manual computer-assisted image analysis as well as a fully automated analysis pathway utilizing a newly developed computer algorithm. Flow velocity was assessed using space-time diagrams of the venules as well as the algorithm-based calculation of an average perfused speed indicator (APSI)., Results: No change in all measured parameters was detected after sublingual topical application of ACH. Sublingual topical application of NG however led to an increase in TVD, space-time diagram-derived venular flow velocity and APSI. No difference was detected in heart rate, blood pressure, and cardiac output as measured by echocardiography, as well as in plasma nitric oxide metabolite content before and after the topical application of ACH and NG., Conclusions: In healthy subjects, the sublingual microcirculatory physiological reserve can be assessed non-invasively by topical application of nitroglycerin without affecting systemic circulation.

Donegani, Enrico, Peter Paal, Thomas Küpper, Urs Hefti, Buddha Basnyat, Anna Carceller, Pierre Bouzat, Rianne van der Spek, and David Hillebrandt. Drug use and misuse in the mountains: a UIAA MedCom consensus guide for medical professionals. High Alt Med Biol. 17:157-184, 2016.-Aims: The aim of this review is to inform mountaineers about drugs commonly used in mountains. For many years, drugs have been used to enhance performance in mountaineering. It is the UIAA (International Climbing and Mountaineering Federation-Union International des Associations d'Alpinisme) Medcom's duty to protect mountaineers from possible harm caused by uninformed drug use. The UIAA Medcom assessed relevant articles in scientific literature and peer-reviewed studies, trials, observational studies, and case series to provide information for physicians on drugs commonly used in the mountain environment. Recommendations were graded according to criteria set by the American College of Chest Physicians., Results: Prophylactic, therapeutic, and recreational uses of drugs relevant to mountaineering are presented with an assessment of their risks and benefits., Conclusions: If using drugs not regulated by the World Anti-Doping Agency (WADA), individuals have to determine their own personal standards for enjoyment, challenge, acceptable risk, and ethics. No system of drug testing could ever, or should ever, be policed for recreational climbers. Sponsored climbers or those who climb for status need to carefully consider both the medical and ethical implications if using drugs to aid performance. In some countries (e.g., Switzerland and Germany), administrative systems for mountaineering or medication control dictate a specific stance, but for most recreational mountaineers, any rules would be unenforceable and have to be a personal decision, but should take into account the current best evidence for risk, benefit, and sporting ethics.

Purpose: Hypoxia and oxidative stress affect endothelial function. Endothelial microparticles (MP) are established measures of endothelial dysfunction and influence vascular reactivity. To evaluate the effects of hypoxia and antioxidant supplementation on endothelial MP profiles, a double-blind, placebo-controlled trial, during a high altitude expedition was performed., Methods: 29 participants were randomly assigned to a treatment group (n = 14), receiving vitamin E, C, A, and N-acetylcysteine daily, and a control group (n = 15), receiving placebo. Blood samples were obtained at 490 m (baseline), 3530, 4590, and 6210 m. A sensitive tandem mass spectrometry method was used to measure 8-iso-prostaglandin F2α and hydroxyoctadecadienoic acids as markers of oxidative stress. Assessment of MP profiles including endothelial activation markers (CD62+MP and CD144+MP) and cell apoptosis markers (phosphatidylserine+MP and CD31+MP) was performed using a standardized flow cytometry-based protocol., Results: 15 subjects reached all altitudes and were included in the final analysis. Oxidative stress increased significantly at altitude. No statistically significant changes were observed comparing baseline to altitude measurements of phosphatidylserine expressing MP (p = 0.1718) and CD31+MP (p = 0.1305). Compared to baseline measurements, a significant increase in CD62+MP (p = 0.0079) and of CD144+MP was detected (p = 0.0315) at high altitudes. No significant difference in any MP level or oxidative stress markers were found between the treatment and the control group., Conclusion: Hypobaric hypoxia is associated with increased oxidative stress and induces a significant increase in CD62+ and CD144+MP, whereas phosphatidylserine+MP and CD31+MP remain unchanged. This indicates that endothelial activation rather than an apoptosis is the primary factor of hypoxia induced endothelial dysfunction.

Background: Findings of cerebral cortical atrophy, white matter lesions and microhemorrhages have been reported in high-altitude climbers. The aim of this study was to evaluate structural cerebral changes in a large cohort of climbers after an ascent to extreme altitudes and to correlate these findings with the severity of hypoxia and neurological signs during the climb., Methods: Magnetic resonance imaging (MRI) studies were performed in 38 mountaineers before and after participating in a high altitude (7126 m) climbing expedition. The imaging studies were assessed for occurrence of new WM hyperintensities and microhemorrhages. Changes of partial volume estimates of cerebrospinal fluid, grey matter, and white matter were evaluated by voxel-based morphometry. Arterial oxygen saturation and acute mountain sickness scores were recorded daily during the climb., Results: On post-expedition imaging no new white matter hyperintensities were observed. Compared to baseline testing, we observed a significant cerebrospinal fluid fraction increase (0.34% [95% CI 0.10-0.58], p = 0.006) and a white matter fraction reduction (-0.18% [95% CI -0.32--0.04], p = 0.012), whereas the grey matter fraction remained stable (0.16% [95% CI -0.46-0.13], p = 0.278). Post-expedition imaging revealed new microhemorrhages in 3 of 15 climbers reaching an altitude of over 7000 m. Affected climbers had significantly lower oxygen saturation values but not higher acute mountain sickness scores than climbers without microhemorrhages., Conclusions: A single sojourn to extreme altitudes is not associated with development of focal white matter hyperintensities and grey matter atrophy but leads to a decrease in brain white matter fraction. Microhemorrhages indicative of substantial blood-brain barrier disruption occur in a significant number of climbers attaining extreme altitudes.

Objectives: Exposure to high altitudes is associated with oxidative cellular damage due to the increased level of reactive oxygen and nitrogen species and altered activity of antioxidant systems. Subjects were submitted to prolonged hypoxia, to evaluate changes in mitochondrial enzyme activities of monocytes and their attenuation by supplementation with antioxidants., Methods: Twelve subjects were randomly assigned to receive antioxidant supplements or placebo prior to and during an expedition to Pik Lenin (7145 m). Monocytes were isolated from blood samples to determine the activity of mitochondrial enzymes cytochrome c oxidase and citrate synthase at 490 m (baseline) and at the altitudes of 3550 m, 4590 m, and 5530 m., Results: An increase in citrate synthase activity at all altitudes levels was observed. Hypoxia induced an increase in the activity of cytochrome c oxidase only at 4590 m. Neither citrate synthase activity nor cytochrome c oxidase activity differed between the subjects receiving antioxidant supplements and those receiving placebo., Conclusions: Hypoxia leads to an increase in citrate synthase activity of monocyte mitochondria as a marker of mitochondrial mass, which is not modified by antioxidant supplementation. The increase in mitochondrial mass may represent a compensatory mechanism to preserve oxidative phosphorylation of monocytes at high altitudes.

Increased pulmonary artery pressure is a well-known phenomenon of hypoxia and is seen in patients with chronic pulmonary diseases, and also in mountaineers on high altitude expedition. Different mediators are known to regulate pulmonary artery vessel tone. However, exact mechanisms are not fully understood and a multimodal process consisting of a whole panel of mediators is supposed to cause pulmonary artery vasoconstriction. We hypothesized that increased hypoxemia is associated with an increase in vasoconstrictive mediators and decrease of vasodilatators leading to a vasoconstrictive net effect. Furthermore, we suggested oxidative stress being partly involved in changement of these parameters. Oxygen saturation (Sao2) and clinical parameters were assessed in 34 volunteers before and during a Swiss research expedition to Mount Muztagh Ata (7549 m) in Western China. Blood samples were taken at four different sites up to an altitude of 6865 m. A mass spectrometry-based targeted metabolomic platform was used to detect multiple parameters, and revealed functional impairment of enzymes that require oxidation-sensitive cofactors. Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 to 0.14 at 6265 m), indicating lower NO availability resulting in less vasodilatative activity. Correspondingly, an increase in systemic oxidative stress was found with a significant increase of the percentage of methionine sulfoxide from a median 6% under normoxic condition to a median level of 30% (p<0.001) in camp 1 at 5533 m. Furthermore, significant increase in vasoconstrictive mediators (e.g., tryptophan, serotonin, and peroxidation-sensitive lipids) were found. During ascent up to 6865 m, significant altitude-dependent changes in multiple vessel-tone modifying mediators with excess in vasoconstrictive metabolites could be demonstrated. These changes, as well as highly significant increase in systemic oxidative stress, may be predictive for increase in acute mountain sickness score and changes in Sao2.

We tested whether the better subjective exercise tolerance perceived by mountaineers after altitude acclimatization relates to enhanced exercise economy. Thirty-two mountaineers performed progressive bicycle exercise to exhaustion at 490 m and twice at 5533 m (days 6-7 and day 11), respectively, during an expedition to Mt. Muztagh Ata. Maximal work rate (W(max)) decreased from mean ± SD 356 ± 73 watts at 490 m to 191 ± 49 watts and 193 ± 45 watts at 5533 m, days 6-7 and day 11, respectively; corresponding maximal oxygen uptakes (VO2max ) were 50.7 ± 9.5, 26.3 ± 5.6, 24.7 ± 7.0 mL/min/kg (P = 0.0001 5533 m vs 490 m). On days 6-7 (5533 m), VO(2) at 75% W(max) (152 ± 37 watts) was 1.75 ± 0.45 L/min, oxygen saturation 68 ± 8%. On day 11 (5533 m), at the same submaximal work rate, VO(2) was lower (1.61 ± 0.47 L/min, P < 0.027) indicating improved net efficiency; oxygen saturation was higher (74 ± 7%, P < 0.0004) but ratios of VO(2) to work rate increments remained unchanged. On day 11, mountaineers climbed faster from 4497 m to 5533 m than on days 5-6 but perceived less effort (visual analog scale 50 ± 15 vs 57 ± 20, P = 0.006) and reduced symptoms of acute mountain sickness. We conclude that the better performance and subjective exercise tolerance after acclimatization were related to regression of acute mountain sickness and improved submaximal exercise economy because of lower metabolic demands for non-external work-performing functions., (© 2011 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Impairment of cognitive performance during and after high-altitude climbing has been described in numerous studies and has mostly been attributed to cerebral hypoxia and resulting functional and structural cerebral alterations. To investigate the hypothesis that high-altitude climbing leads to cognitive impairment, we used of neuropsychological tests and measurements of eye movement (EM) performance during different stimulus conditions. The study was conducted in 32 mountaineers participating in an expedition to Muztagh Ata (7,546 m). Neuropsychological tests comprised figural fluency, line bisection, letter and number cancellation, and a modified pegboard task. Saccadic performance was evaluated under three stimulus conditions with varying degrees of cortical involvement: visually guided pro- and anti-saccades, and visuo-visual interaction. Typical saccade parameters (latency, mean sequence, post-saccadic stability, and error rate) were computed off-line. Measurements were taken at a baseline level of 440 m and at altitudes of 4,497, 5,533, 6,265, and again at 440 m. All subjects reached 5,533 m, and 28 reached 6,265 m. The neuropsychological test results did not reveal any cognitive impairment. Complete eye movement recordings for all stimulus conditions were obtained in 24 subjects at baseline and at least two altitudes and in 10 subjects at baseline and all altitudes. Measurements of saccade performances showed no dependence on any altitude-related parameter and were well within normal limits. Our data indicates that acclimatized climbers do not seem to suffer from significant cognitive deficits during or after climbs to altitudes above 7,500 m. We demonstrated that investigation of EMs is feasible during high-altitude expeditions.

High altitude periodic breathing (PB) shares some common pathophysiologic aspects with sleep apnea, Cheyne-Stokes respiration and PB in heart failure patients. Methods that allow quantifying instabilities of respiratory control provide valuable insights in physiologic mechanisms and help to identify therapeutic targets. Under the hypothesis that high altitude PB appears even during physical activity and can be identified in comparison to visual analysis in conditions of low SNR, this study aims to identify PB by characterizing the respiratory pattern through the respiratory volume signal. A number of spectral parameters are extracted from the power spectral density (PSD) of the volume signal, derived from respiratory inductive plethysmography and evaluated through a linear discriminant analysis. A dataset of 34 healthy mountaineers ascending to Mt. Muztagh Ata, China (7,546 m) visually labeled as PB and non periodic breathing (nPB) is analyzed. All climbing periods within all the ascents are considered (total climbing periods: 371 nPB and 40 PB). The best crossvalidated result classifying PB and nPB is obtained with Pm (power of the modulation frequency band) and R (ratio between modulation and respiration power) with an accuracy of 80.3% and area under the receiver operating characteristic curve of 84.5%. Comparing the subjects from 1(st) and 2(nd) ascents (at the same altitudes but the latter more acclimatized) the effect of acclimatization is evaluated. SaO(2) and periodic breathing cycles significantly increased with acclimatization (p-value &#60; 0.05). Higher Pm and higher respiratory frequencies are observed at lower SaO(2), through a significant negative correlation (p-value &#60; 0.01). Higher Pm is observed at climbing periods visually labeled as PB with > 5 periodic breathing cycles through a significant positive correlation (p-value &#60; 0.01). Our data demonstrate that quantification of the respiratory volume signal using spectral analysis is suitable to identify effects of hypobaric hypoxia on control of breathing.

Objectives: The Commission gives recommendations on how to provide health and safety for employees in different kinds of low oxygen atmospheres. So far, no recommendations exist that take into account the several factors we have outlined in this report., Methods: The health and safety recommendations of several countries were analysed for their strength and deficiencies. The scientific literature was checked (Medline, etc.) and evaluated for relevance of the topic. Typical situations of work in hypoxia were defined and their specific risks described. Specific recommendations are provided for any of these situations., Results: We defined four main groups with some subgroups (main risk in brackets): short exposure (pressure change), limited exposure (acute altitude disease), expatriates (chronic altitude disease), and high-altitude populations (re-entry pulmonary oedema). For healthy unacclimatized persons, an acute but limited exposure down to 13% O(2) does not cause a health risk. Employees should be advised to leave hypoxic areas for any break, if possible. Detailed advice is given for any other situation and pre-existing diseases., Conclusions: If the specific risk of the respective type of hypoxia is taken into account, a pragmatic approach to provide health and safety for employees is possible. In contrast to other occupational exposures, a repeated exposure as often as possible is of benefit as it causes partial acclimatization. The consensus statement was approved by written consent in lieu of a meeting in July 2009.

Objective: Variations in definitions, scores, and methodologies have created differences in the results and conclusions obtained from studies on mountaineering and climbing sports injuries and illnesses; this has made interstudy comparisons difficult or impossible. To develop a common, simple, and sport-specific scoring system to classify injuries and illnesses in mountaineering and climbing studies; such retrospective scoring would facilitate the analysis and surveillance of their frequencies, severity and fatalities, and outcomes of any treatment., Methods: The UIAA (The International Mountaineering and Climbing Federation) makes recommendations, sets policy, and advocates on behalf of the climbing and mountaineering community internationally through its various commissions. Using a nominal group consensus model approach, a working group was formed during the UIAA Medical Commission's meeting in Adršpach - Zdoňov, in the Czech Republic, 2008. This group critically examined climbing and other relevant literature for various methodological approaches in measuring injury incident rates and severity, including data sources, and produced a working document that was later edited and ratified by all members of the UIAA Medical Commission., Results: Definitions of injury location, injury classification, and fatality risk are proposed. Case fatality, time-related injury risk, and a standardized metric climbing difficulty scale are also defined., Conclusions: The medical commission of the UIAA recommends the use of the described criteria and scores for future research in mountaineering and climbing sports in order to enable robust and comprehensive interstudy comparisons and epidemiological analysis., (Copyright © 2011 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Background: Retinal hemorrhages have been described as a component of high altitude retinopathy (HAR) in association with altitude illness. In this prospective high altitude study, we aimed to gain new insights into the pathophysiology of HAR and explored whether HAR could be a valid early indicator of altitude illness., Methodology/principal Findings: 28 mountaineers were randomly assigned to two ascent profiles during a research expedition to Mt. Muztagh Ata (7546 m/24,751 ft). Digital fundus photographs were taken prior to expedition at 490 m (1,607 ft), during expedition at 4497 m (14,750 ft = base camp), 5533 m (18,148 ft), 6265 m (20,549 ft), 6865 m (22,517 ft) and 4.5 months thereafter at 490 m. Number, size and time of occurrence of hemorrhages were recorded. Oxygen saturation (SpO₂) and hematocrit were also assessed. 79% of all climbers exhibited retinal hemorrhages during the expedition. Number and area of retinal bleeding increased moderately to medium altitudes (6265 m). Most retinal hemorrhages were detected after return to base camp from a high altitude. No post-expeditional ophthalmic sequelae were detected. Significant negative (SpO₂ Beta: -0.4, p<0.001) and positive (hematocrit Beta: 0.2, p = 0.002, time at altitude Beta: 0.33, p = 0.003) correlations with hemorrhages were found., Conclusions/significance: When closely examined, a very large amount of climbers exhibit retinal hemorrhages during exposure to high altitudes. The incidence of retinal hemorrhages may be greater than previously appreciated as a definite time lag was observed between highest altitude reached and development of retinal bleeding. Retinal hemorrhages should not be considered warning signs of impending severe altitude illness due to their delayed appearance.

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).

Purpose: Reports on intraocular pressure (IOP) changes at high altitudes have provided inconsistent and even conflicting, Results: The purpose of this study was to investigate the effect of very high altitude and different ascent profiles on IOP in relation to simultaneously occurring ophthalmic and systemic changes in a prospective study., Methods: This prospective study involved 25 healthy mountaineers who were randomly assigned to two different ascent profiles during a medical research expedition to Mt. Muztagh Ata (7,546 m/24,751 ft). Group 1 was allotted a shorter acclimatization time before ascent than was group 2. Besides IOP, oxygen saturation (SaO(2)), acute mountain sickness symptoms (AMS-c score), and optic disc appearance were assessed. Examinations were performed at 490 m/1,607 ft, 4,497 m/14,750 ft, 5,533 m/18,148 ft, and 6,265 m/20,549 ft above sea level., Results: Intraocular pressure in both groups showed small but statistically significant changes: an increase during ascent from 490 m/1,607 ft to 5,533 m/18,148 ft and then a continuous decrease during further ascent to 6,265 m/20,549 ft and on descent to 4,497 m/14,750 ft and to 490 m. Differences between groups were not significant. Multiple regression analysis (IOP-dependent variable) revealed a significant partial correlation coefficient of beta = -0.25 (P = 0.01) for SaO(2) and beta = -0.23 (P = 0.02) for acclimatization time., Discussion: Hypobaric hypoxia at very high altitude leads to small but statistically significant changes in IOP that are modulated by systemic oxygen saturation. Climbs to very high altitudes seem to be safe with regard to intraocular pressure changes.

Principles: Data on changes of haemostatic parameters at altitudes above 5000 m are very limited. So far it is unknown, whether altered coagulation could contribute to the development of acute mountain sickness., Methods: Thirty four healthy mountaineers were randomised to two acclimatisation protocols and undertook an expedition on Muztagh Ata (7549 m) in China. Tests were performed at five altitudes up to 6865 m. Haemostatic parameters, such as PT, aPTT, D-Dimer, APC-Resistance (APCR), von Willebrand Factor activity (RCo), ADAMTS-13 & C-Natriuretic Peptide (CNP) were assessed together with Lake Louise AMS score., Results: D-Dimer significantly increased with increasing altitude (median 0.62 to 0.81 mcg/L, p <0.0001). During ascent, PT increased (83% to >100%) and APCR decreased significantly from 0.95 to 0.8 (p <0.01). Furthermore, a significant increase of aPTT (38 to 43 sec) was paralleled by significant changes of RCo (102% to 62%) (both p <0.001). There were no significant changes in ADAMTS-13 and CNP. No significant relationship between investigated parameters and AMS scores could be detected. When comparing the participants of the two acclimatisation protocols, there was an overall higher RCo in patients with a faster ascent protocol (p = 0.04). This was accompanied by lower ADAMTS-13 of the coagulation system in these patients (p = 0.04)., Conclusions: Coagulation parameters change significantly during hypobaric hypoxia. Whereas we could detect no association between AMS scores and coagulation parameters, our results do show some parameters to be associated with an acclimatisation protocol and a successful ascent to the summit.

Objective: To investigate the effect of very high altitude and different ascent profiles on central corneal thickness (CCT)., Methods: Twenty-eight healthy mountaineers were randomly assigned to 2 different ascent profiles during a medical research expedition to Mount Muztagh Ata (7546 m) in western China. Group 1 was allotted a shorter acclimatization time prior to ascent to 6265 m. The main outcome measure was CCT. Secondary outcome measures were oxygen saturation (SpO(2)) and symptom assessments of acute mountain sickness (cerebral acute mountain sickness score). Examinations were performed at 490, 4497, 5533, and 6265 m., Results: Central corneal thickness increased in both groups with increasing altitude and decreased after descent. In group 1 (with the shorter acclimatization), mean CCT increased from 537 to 572 microm. Mean CCT in group 2 increased from 534 to 563 microm (P = .048). The amount of decrease in SpO(2) paralleled the increase in CCT. There was no significant decrease in visual acuity. There was a significant correlation between CCT and cerebral acute mountain sickness score when controlled for SpO(2) and age., Conclusions: Corneal swelling during high-altitude climbs is promoted by low SpO(2). Systemic delivery of oxygen to the anterior chamber seems to play a greater role in corneal oxygenation than previously thought. Adhering to a slower ascent profile results in less corneal edema. Visual acuity in healthy corneas is not adversely affected by edema at altitudes of up to 6300 m. Individuals with more acute mountain sickness-related symptoms had thicker corneas, possibly due to their higher overall susceptibility to hypoxia.

Bloch, Konrad E., Alexander J. Turk, Marco Maggiorini, Thomas Hess, Tobias Merz, Martina M. Bosch, Daniel Barthelmes, Urs Hefti, Jacqueline Pichler, Oliver Senn, and Otto D. Schoch. Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m. High Alt. Med. Biol. 10:25-32, 2009.-Data on acclimatization during expedition-style climbing to > 5000 m are scant. We evaluated the hypothesis that minor differences in ascent protocol influence acute mountain sickness (AMS) symptoms and mountaineering success in climbers to Muztagh Ata (7546 m), Western China. We performed a randomized, controlled trial during a high altitude medical research expedition to Muztagh Ata. Thirty-four healthy mountaineers (mean age 45 yr, 7 women) were randomized to follow one of two protocols, ascending within 15 or 19 days to the summit of Muztagh Ata at 7546 m, respectively. The main outcome measures, AMS symptom scores and the number of proceeding climbers, were assessed daily. Mean +/- SD AMS-C scores of 16 climbers randomized to slow ascent were 0.06 +/- 0.18, 0.26 +/- 0.08, 0.41 +/- 0.45, 0.53 +/- 0.77 at camps I (5533 m), II (6265 m), III (6865 m), and the summit (7546 m), respectively. Corresponding values in 18 climbers randomized to fast ascent were significantly higher: 0.17 +/- 0.23, 0.43 +/- 0.75, 0.49 +/- 0.36, and 0.69 +/- 0.54 (p < 0.008, vs. slow ascent in regression analysis accounting for weather-related protocol deviation). Climbers randomized to slow ascent were able to ascend according to the protocol without AMS for significantly more days than climbers randomized to fast ascent (p = 0.04, Kaplan-Meier analysis). More climbers randomized to slow ascent were successful in reaching the highest camp at 6865 m without AMS (odds ratio 9.5; 95% confidence interval 1.02 to 89). In climbers ascending to very high altitudes, differences of a few days in acclimatization have a significant impact on symptom severity, the prevalence of AMS, and mountaineering success. ClinicalTrials.gov Identifier NCT00603122.

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

Objectives: To determine the incidence of optic disc swelling as a possible indicator of cerebral edema in a large group of healthy mountaineers exposed to very high altitudes and to correlate these findings with various clinical and environmental factors and occurrence of acute mountain sickness and high-altitude cerebral edema., Methods: This multidisciplinary, prospective, observational cohort study was performed in 2005 within the scope of a medical research expedition to Muztagh Ata (7546 m [24,751 ft]) in Western Xinjiang Province, China. Twenty-seven healthy mountaineers aged 26 to 62 years participated. Medical examinations were performed in Switzerland 1 month before and 4 1/2 months after the expedition. Ophthalmologic examinations were performed at 4 high camps (maximum elevation, 6865 m [22,517 ft]). Optic disc status was documented using digital photography. Further assessments included arterial oxygen saturation and cerebral acute mountain sickness scores., Results: Sixteen of 27 study subjects (59%) exhibited optic disc swelling during their stay at high altitudes, with complete regression on return to lowlands. Significant correlation was noted between optic disc swelling and lower arterial oxygen saturation (odds ratio, 0.86 per percentage of arterial oxygen saturation; 95% confidence interval, 0.81-0.92; P < .001), younger age (odds ratio, 0.95 per year; 95% confidence interval, 0.90-0.99; P = .03), and higher cerebral acute mountain sickness scores (odds ratio, 2.32 per 0.1 point; 95% confidence interval, 1.48-3.63; P < .001)., Conclusion: Optic disc swelling occurs frequently in high-altitude climbers and is correlated with peripheral oxygen saturation and symptoms of acute mountain sickness. It is most likely the result of hypoxia-induced brain volume increase.

Aim: Acute mountain sickness (AMS) can result in pulmonary and cerebral oedema with overperfusion of microvascular beds, elevated hydrostatic capillary pressure, capillary leakage and consequent oedema as pathogenetic mechanisms. Data on changes in glomerular filtration rate (GFR) at altitudes above 5000 m are very limited., Methods: Thirty-four healthy mountaineers, who were randomized to two acclimatization protocols, undertook an expedition on Muztagh Ata Mountain (7549 m) in China. Tests were performed at five altitudes: Zurich pre-expedition (PE, 450 m), base camp (BC, 4497 m), Camp 1 (C1, 5533 m), Camp 2 (C2, 6265 m) and Camp 3 (C3, 6865 m). Cystatin C- and creatinine-based (Mayo Clinic quadratic equation) GFR estimates (eGFR) were assessed together with Lake Louise AMS score and other tests., Results: eGFR significantly decreased from PE to BC (P < 0.01). However, when analysing at changes between BC and C3, only cystatin C-based estimates indicated a significant decrease in GFR (P = 0.02). There was a linear decrease in eGFR from PE to C3, with a decrease of approx. 3.1 mL min(-1) 1.73 m(-2) per 1000 m increase in altitude. No differences between eGFR of the two groups with different acclimatization protocols could be observed. There was a significant association between eGFR and haematocrit (P = 0.01), whereas no significant association between eGFR and aldosterone, renin and brain natriuretic peptide could be observed. Finally, higher AMS scores were significantly associated with higher eGFR (P = 0.01)., Conclusions: Renal function declines when ascending from low to high altitude. Cystatin C-based eGFR decreases during ascent in high altitude expedition but increases with AMS scores. For individuals with eGFR <40 mL min(-1) 1.73 m(-2), caution may be necessary when planning trips to high altitude above 4500 m above sea level.

The possibility of persistent cerebral impairment due to exposure to extreme altitude and resulting hypoxic conditions is of great concern to both high altitude mountaineers and researchers. The aim of the present study was to investigate the effect of prolonged exposure to hypoxia on cerebral glucose metabolism, which probably precedes structural and functional impairment. Positron emission tomography (PET) employing [18F]-2-deoxy-2-fluoro-D-glucose (FDG) was performed, and the normobaric hypoxic ventilatory response (HVR) was assessed in 11 mountaineers before (pre) and after (post) climbing Mount Shisha Pangma (8048 m). During the climb, acute mountain sickness (AMS) symptoms were recorded and heart rate and oxygen saturation (SaO2) were measured daily. Neuropsychological evaluations were conducted at different heights. The difference FDGpost- FDGpre was analyzed voxel by voxel using statistical parametric mapping (SPM) and volumes of interest (VOI). SPM revealed two areas of increased cerebral FDG uptake after the expedition, one localized in the left cerebellum (+9.4%) and one in the white matter lateral of the left thalamus (+8.3%). The VOI analysis revealed increased postexpeditional metabolism in an area of the right cerebellum (+11%) and of the thalamus bilaterally (+3.7% on the left, +4.6% on the right). FDG-PET alterations did not correlate with changes in SaO2, HVR, or AMS scores. All neuropsychological test results during the climb were unremarkable. We conclude that a prolonged stay at an extreme altitude leads to regional specific changes in the cerebral glucose metabolism without any signs of neuropsychological impairment during the climb.