High altitude retinopathy: An overview and new insights.

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.

Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update.

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention, diagnosis, and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. Recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches for managing each form of acute altitude illness that incorporate these recommendations as well as recommendations on how to approach high altitude travel following COVID-19 infection. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in Wilderness & Environmental Medicine in 2010 and the subsequently updated WMS Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness published in 2014 and 2019.

Sherpas, Coca Leaves, and Planes: High Altitude and Airplane Headache Review with a Case of Post-LASIK Myopic Shift.

PURPOSE OF REVIEW: High altitude headache is a common neurological symptom that is associated with ascent to high altitude. It is classified by the International Classification of Headache Disorders, 3rd Edition (ICHD-3) as a disorder of homeostasis. In this article, we review recent clinical and insights into the pathophysiological mechanisms of high altitude and airplane headache. We also report a second case of post-LASIK myopic shift at high altitude exposure secondary hypoxia. Headache attributed to airplane travel is a severe typically unilateral orbital headache that usually improves after landing. This was a relative recent introduction to the ICHD-3 diagnostic criteria. Headache pain with flight travel has long been known and may have been previously considered as a part of barotrauma. Recent studies have helped identify this as a distinct headache disorder. RECENT FINDINGS: Physiologic, hematological, and biochemical biomarkers have been identified in recent high altitude studies. There have been recent advance in identification of molecular mechanisms underlying neurophysiologic changes secondary to hypoxia. Calcitonin gene-related peptide, a potent vasodilator, has been implicated in migraine pathophysiology. Recent epidemiological studies indicate that the prevalence of airplane headache may be more common than we think in the adult as well at the pediatric population. Simulated flight studies have identified potential biomarkers. Although research is limited, there have been advances in both clinical and pathophysiological mechanisms associated with high altitude and airplane headache.

Acute hemodynamic changes by breathing hypoxic and hyperoxic gas mixtures in pulmonary arterial and chronic thromboembolic pulmonary hypertension.

BACKGROUND: There is insufficient evidence to counsel patients with pulmonary hypertension undergoing altitude or air travel. We thus aimed to study hemodynamic response of patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH) during changes in inspiratory oxygen partial pressure. METHODS AND RESULTS: Consecutive patients undergoing right heart catheterization had hemodynamic assessments whilst breathing ambient air (normoxia, FiO2 0.21, at altitude 490 m), nitrogen-enriched air (hypoxia, FiO2 0.16, simulated altitude 2600 m) and oxygen (hyperoxia, FiO2 1.0), each for 10 min. Data from patients with PAH/CTEPH with mean pulmonary artery pressure (mPAP) ≥25 mmHg, pulmonary artery wedge pressure ≤15 mmHg, were compared to data from controls, mPAP <20 mmHg. 28 PAH/CTEPH-patients, 15 women, median age (quartiles) 62y (49;73), mPAP 35 mmHg (31;44), PaO2 7.1 kPa (6.8;9.3) and 16 controls, 12 women, 60y (52;69), mPAP 18 mmHg (16;18), PaO2 9.5 kPa (8.5;10.6) were included. Hypoxia reduced the PaO2 in PAH/CTEPH-patients by median of 2.3 kPa, in controls by 3.3 kPa, difference (95%CI) in change 1.0 (0.02 to 1.9), p < 0.05. Corresponding changes in pulmonary vascular resistance, mPAP and cardiac output were nonsignificant in both groups. Hyperoxia decreased mPAP in PAH/CTEPH-patients by 4 mmHg (2 to 6), in controls by 2 mmHg (0 to 3), difference in change 3 mmHg (0 to 5), p < 0.05. CONCLUSIONS: In patients with PAH/CTEPH, very short-term exposure to moderate hypoxia similar to 2600 m altitude or during commercial air travel did not deteriorate hemodynamics. These results encourage studying the response of PAH/CTEPH during daytrips to the mountain or air travel.

Pharmacological interventions for preventing acute mountain sickness: a network meta-analysis and trial sequential analysis of randomized clinical trials.

BACKGROUND: Individuals ascending to high altitude are at a risk of getting acute mountain sickness (AMS). The present study is a network meta-analysis comparing all the interventions available to prevent AMS. METHODS: Electronic databases were searched for randomized clinical trials evaluating the use of drugs to prevent AMS. Incidence of AMS was the primary outcome and incidence of severe AMS, paraesthesia (as side effect of acetazolamide use), headache and severe headache, and oxygen saturation were the secondary outcomes. Odds ratio [95% confidence interval] was the effect estimate for categorical outcomes and weighted mean difference for oxygen saturation. Random effects model was used to derive the direct and mixed treatment comparison pooled estimates. Trial sequential analysis and grading of the evidence for key comparisons were carried out. RESULTS: A total of 24 studies were included. Acetazolamide at 125, 250 and 375 mg twice daily, dexamethasone and ibuprofen had statistically significant lower incidence of AMS compared to placebo. All the above agents except ibuprofen were also observed to significantly reduce the incidence of severe AMS. Acetazolamide alone or in combination with Ginkgo biloba were associated with lower incidence of headache, but higher risk of paraesthesia. Acetazolamide at 125 mg and 375 mg twice daily significantly reduce the incidence of severe headache as like ibuprofen. Trial sequential analysis indicates that the current evidence is adequate for the incidence of AMS only for acetazolamide 125 and 250 mg twice daily. Similarly, the strength of evidence for acetazolamide 125 and 250 mg twice daily was moderate while it was either low or very low for all other comparisons. CONCLUSIONS: Acetazolamide at 125, 250 and 375 mg twice daily, ibuprofen and dexamethasone significantly reduce the incidence of AMS of which adequate evidence exists only for acetazolamide 125 and 250 mg twice daily therapy. Acetazolamide 125 mg twice daily could be the best in the pool considering the presence of enough evidence for preventing AMS and associated with lower incidence of paraesthesia. Key messages Acetazolamide 125, 250 and 375 mg twice daily, dexamethasone and ibuprofen reduce the incidence of AMS in high altitudes. Adequate evidence exists supporting the use of acetazolamide 125 mg and 250 mg twice daily for preventing AMS of which acetazolamide 125 mg twice daily could be the best.

Dietary nitrate supplementation increases acute mountain sickness severity and sense of effort during hypoxic exercise.

Dietary nitrate supplementation enhances sea level performance and may ameliorate hypoxemia at high altitude. However, nitrate may exacerbate acute mountain sickness (AMS), specifically headache. This study investigated the effect of nitrate supplementation on AMS symptoms and exercise responses with 6-h hypoxia. Twenty recreationally active men [age, 22 ± 4 yr, maximal oxygen consumption (V̇o2max), 51 ± 6 ml·min-1·kg-1, means ± SD] completed this randomized double-blinded placebo-controlled crossover study. Twelve participants were classified as AMS- on the basis of Environmental Symptoms Questionnaire [Acute Cerebral Mountain Sickness score (AMS-C)] <0.7 in both trials, and five participants were classified as AMS+ on the basis of AMS-C ≥0.7 on placebo. Five days of nitrate supplementation (70-ml beetroot juice containing ~6.4 mmol nitrate daily) increased plasma NO metabolites by 182 µM compared with placebo but did not reduce AMS or improve exercise performance. After 4-h hypoxia [inspired O2 fraction ([Formula: see text]) = 0.124], nitrate increased AMS-C and headache severity (visual analog scale; whole sample ∆10 [1, 20] mm, mean difference [95% confidence interval]; P = 0.03) compared with placebo. In addition, after 5-h hypoxia, nitrate increased sense of effort during submaximal exercise (∆7 [-1, 14]; P = 0.07). In AMS-, nitrate did not alter headache or sense of effort. In contrast, in AMS+, nitrate increased headache severity (∆26 [-3, 56] mm; P = 0.07), sense of effort (∆14 [1, 28]; P = 0.04), oxygen consumption, ventilation, and mean arterial pressure during submaximal exercise. On the next day, in a separate acute hypoxic exercise test ([Formula: see text] = 0.141), nitrate did not improve time to exhaustion at 80% hypoxic V̇o2max In conclusion, dietary nitrate increases AMS and sense of effort during exercise, particularly in those who experience AMS. Dietary nitrate is therefore not recommended as an AMS prophylactic or ergogenic aid in nonacclimatized individuals at altitude.NEW & NOTEWORTHY This is the first study to identify that the popular dietary nitrate supplement (beetroot) does not reduce acute mountain sickness (AMS) or improve exercise performance during 6-h hypoxia. The consumption of nitrate in those susceptible to AMS exacerbates AMS symptoms (headache) and sense of effort and raises oxygen cost, ventilation, and blood pressure during walking exercise in 6-h hypoxia. These data question the suitability of nitrate supplementation during altitude travel in nonacclimatized people.

[Development of a methodology of for medical-flight examination of flight personnel under condition of hospital].

Development of a methodology of for medical-flight examination of flight personnel under condition of hospital. When performing an experimental study of ways of improvement of hyperbaric ascent involving 95 servicemen,of special contingent determined lack of ascent security of flight crews to altitudes up to 6500 meters due to the large percentage (10%) of revealed reduced hypoxia tolerance of mild and moderate level in military personnel and potentially high risk of high-altitude decompression disease without a preparatory desaturation. The experimental testing of 5 minutes ascent technique for 5000 m and 6000 m is performed, justified criteria of hypobaric hypoxia tolerance of mild and moderate level during the examination of health state of 589 aircrew personnel (including personnel with approved diagnoses) in hyperbaric chamber in relation to hospital conditions. It is experimentally shown that the method of the survey in the chamber on hypoxia tolerance of mild and moderate level in the ascent to the height of 5000 m and 6000 m is an effective mean of determining the functional state and reserve capacity of the organism to identify hidden forms of human diseases and can be used for medical-flight examination of flight personnel in a hospital.

Altitude headache.

High altitude headache (HAH) has been defined by the International Headache Society as a headache that appears within 24 hours after ascent to 2,500 m or higher [1••]. The headache can appear in isolation or as part of acute mountain sickness (AMS), which has more dramatic symptoms than the headache alone. If symptoms are ignored, more serious conditions such as high altitude cerebral edema (HACE), high altitude pulmonary edema (HAPE), or even death may ensue. While there is no definitive understanding of the underlying pathophysiologic mechanism, it is speculated that HAH occurs from the combination of hypoxemia-induced intracranial vasodilation and subsequent cerebral edema. There are a number of preventive measures that can be adopted prior to ascending, including acclimatization and various medications. A variety of pharmacological interventions are also available to clinicians to treat this extremely widespread condition.

High-altitude pulmonary edema: diagnosis, prevention, and treatment.

High-altitude pulmonary edema (HAPE) is a lethal, noncardiogenic form of pulmonary edema that afflicts susceptible individuals after rapid ascent to high altitude above 2,500 m. Prevention of HAPE is achieved most effectively by gradual ascent allowing time for proper acclimatization. Certain prophylactic medications may further reduce the risk of ascending to high altitude in individuals with a prior history of HAPE. The most effective and reliable treatment of HAPE is immediate descent and administration of supplemental oxygen.

Tibetan plateau earthquake: altitude challenges to medical rescue work.

BACKGROUND: Rescue efforts for earthquakes in remote plateau regions require large numbers of professional personnel to be transported from various lowland regions for relief work. Unacclimatised rescuers to high-altitude regions commonly suffer acute mountain sickness (AMS), which makes relief efforts inefficient and potentially dangerous. METHODS: In this study, the AMS symptoms of 78 unacclimatised rescue workers for the Yushu earthquake from Beijing were recorded using the Lake Louise AMS self-report questionnaire. Heart rate and blood oxygen were recorded at rest before departure, during rest and during activity. RESULTS: After ascending, resting heart rate increased from mean 75.87 bpm to 87.45 bpm and resting SpO(2) decreased from an average of 98.51% to 90.35% (both p<0.001). The mean Lake Louise AMS Score for participants was 3.1 (95% CI 2.6 to 3.6). 29 members (37.2%) met the diagnosis criteria for AMS. 16 members (20.5%) were evacuated early due to acute AMS (AMS score ≥5). Rhodiola was offered on a voluntary basis as a prophylactic measure but shown to be ineffective. CONCLUSION: Given the ineffectiveness of prophylactic measures and the urgency of such disaster situations, it is unrealistic to mobilise rescue teams from lowland regions for immediate relief efforts. A local disaster plan specific to plateau earthquakes needs to be developed with local personnel for timely and efficient relief.

High altitude ataxia--its assessment and relevance.

Ataxia at altitude is reviewed in relation to acute mountain sickness (AMS). The cause of ataxia occurring at altitude is unknown but may be hypoxia affecting basal ganglia and hindbrain activity. Ataxia is an important sign of high altitude cerebral edema (HACE) but is less well-established as a clinical feature of AMS. Assessment of ataxia is part of the Environmental Systems and the Lake Louise questionnaires, together with a heel-to-toe measurement. More precise measures of ataxia include the Sharpened Romberg Test (SRT) and the use of unstable platforms. Isolated ataxia at altitude may not be related to AMS or HACE. Age affects ataxia and careful baseline measurements are essential in older subjects before results at high altitude can be interpreted. Testing for ataxia needs to be standardized with sufficient learning time. Ataxia should be distinguished from weakness or fatigue occurring at altitude. Specialized tests have not been shown to be clinically important. Our results above 5000 m showed that an abnormal SRT may be specific for AMS but with relatively poor sensitivity. Wobble board results have not correlated with AMS scores consistently. Other authors using an unstable platform in a chamber and static posturography during 3 days of exposure to 4559 m also found no relationship with AMS scores. Ataxia is a common and important clinical feature of HACE but is unhelpful in the assessment of mild or even moderate AMS in the absence of an altered mental state. The simple heel-to-toe test remains a useful part of the assessment of more severe AMS bordering on HACE.

Impaired glucose regulation in a Sherpa indigenous population living in the Everest region of Nepal and in Kathmandu Valley.

The aim of this study was to determine the prevalence of impaired glucose regulation status in Sherpa adults living in the Everest area and in Kathmandu valley. A cross-sectional survey was conducted in Chaurikharka village (Everest area) and Kathmandu city on 119 and 121 randomly selected individuals, aged 30-70 years. They were assessed on conventional risk factors for diabetes, and an oral glucose tolerance test was performed. Based on the 2003 American Diabetes Association criteria, the prevalence in the Kathmandu city and Everest region of any impaired glucose regulation (IGR), isolated impaired fasting plasma glucose (isolated IFG), isolated impaired glucose tolerance (isolated IGT), and combined isolated IFG and isolated IGT were 55.4% vs. 23.5%, 42.1% vs. 14.3%, 1.7% vs. 0.8%, 11.6 vs. 8.4%, respectively. Using the subjects with normal glucose tolerance as the referent group and after adjusting for age, sex, physical activity, calories, and waist circumference, the odds ratios for isolated IFG and combined isolated IFG and isolated IGT of living in the highland region were 0.19 (0.08-0.44) and 0.33 (0.09-1.18), respectively. Isolated IFG was more common among the lowland Sherpas. Unlike combined isolated IFG and isolated IGT, this isolated IFG difference could not be explained by the difference of conventional diabetes mellitus risk factors.

[Serious and sometimes fatal consequences of high-altitude pulmonary oedema]. / Ernstige en soms fatale gevolgen van hoogtelongoedeem.

Three women aged 25, 34 and 22 years respectively, experienced high-altitude pulmonary oedema during a climbing holiday. The first patient presented with complaints arising from a fast ascent to high altitude and was treated with acetazolamide and rapid descent. She recovered without any complications. The second patient developed symptoms during the night, which were not recognised as high-altitude pulmonary oedema. The next morning she died while being transported down on a stretcher without having received any medication or oxygen. The third case was not a specific presentation of high-altitude pulmonary oedema but autopsy revealed pulmonary oedema. This woman had already been higher up on the mountain before she developed complications. The cases illustrate the seriousness of this avoidable form of high altitude illness. The current Dutch national guidelines advise against the use of medication by lay people. A revision is warranted: travellers to high altitude should be encouraged to carry acetazolamide, nifedipine and corticosteroids on the trip. Travel guides ought to be trained to use these drugs. In addition climbing travellers should be encouraged to adopt appropriate preventive behaviour and to start descending as soon as signs of high-altitude pulmonary oedema develop.

Principios epistemológicos en investigación aplicadaen salud: a propósito de la investigación de la anemiaferropénica en niños residentes de gran altitud / Epistemological principles in applied research health: a report of the investigation of anemia Iron deficiency in children living in high altitude

Los principios epistemológicos y sus procesos permiten una explicación inductiva, que genera conocimiento científico desde la investigaciónaplicada a gran altitud. Desde la investigación realizada sobre anemia en niños a gran altitud, se presenta un resumen sobre el tema,mostrándose los objetivos y resultados de diferentes estudios.OBJETIVO. Analizar epistemológicamente diferentes estudios. En uno se definió los puntos de corte de anemia ferropénica en niños de 6 meses a 9años de edad y su prevalencia. En otro estudio, se determinó la eficacia de dos estrategias para el control de la anemia: la suplementacióncon hierro y otra el enriquecimiento del Api con hierro.METODOS.La epistemología, utiliza la explicación inductiva y la probabilidad, para obtener conocimiento científico aplicable a niños anémicos de granaltitud. La suplementación con compuestos de hierro actúa como patrón de oro, y permitió obtener puntos de corte que definen la anemiaferropénica y su prevalencia. El segundo estudio estableció la eficacia de la suplementación con hierro en la modalidad diaria vs. semanal,mediante un ensayo clínico controlado aleatorizado, con grupo placebo. Niños y niñas, definidos como anémicos con hemoglobina igual omenor a 144 g/L. El Grupo 1 placebo (n=57), el Grupo 2 sulfato ferroso 1 día por semana (n=58) y el Grupo 3, recibió 5 días por semana(n=58) durante 16 semanas. Estado nutricional evaluado por: peso/talla, peso/edad, talla/edad. El tercer estudio, determinó la eficacia delenriquecimiento del Api con sulfato ferroso vs. otros compuestos de hierro.RESULTADOS.La suplementación con hierro permitió obtener umbrales que definen anemia a gran altitud con una prevalencia de 22.4 - 70...

The epistemiologic principles and their process allow an inductive explanation which generates scientific knowledge beginning from the operational research at high altitude. From the research already conducted on anaemia in children at high altitude we present here the abstract on this subject, showing the objectives and results of the numerous studies.ObjectiveEpistemiological assessment of the different studies. One study defines the cut off points of ferropenic anaemia in children between 6 months and 9 years old, and its prevalence. Another study determines the efficacy of two strategies for the control of anaemia: iron supplementation and iron enrichment of Api.MethodThe epistemiology uses the inductive explanation and probability to obtain applicable scientific knowledge in anaemic children at high altitude. The supplementation with iron compounds acts like a “gold standard” and permitted the obtention of cut off points that define the ferropenic anaemia and its prevalence. The second study established the efficacy of the iron supplementation by the daily vs. weekly modes, by means of a Randomized Blinded Trial with a placebo group. Boys and girls were diagnosed as anaemic children with haemoglobin concentrations egual to or less than 144 g/L. Group 1 received a placebo (n=57), group 2 (n=58) ferrous sulphate 1 day per week, and group 3 (n=58) 5 days per week during 16 weeks. The nutritional status was assessed by weight/height, weight/age, height/age. The third study determined the efficacy of enrichment of Api containing ferrous sulphate vs. other iron compounds.ResultsThe iron supplementation permitted the obtention of cut off points that defined anaemia at high altitude with a prevalence of 22.4 to 70% in children of 6 months to 9 years old. The iron supplementation of 1 day per week has the same efficacy as the 5 days per week supplementation for correcting anaemia...

[Experience of hyperbaric oxygenation treatment of a patrient with acute hypobaropathy].

Five sessions of computerized hyperbaric oxygenation treatment resulted in complete recovery of a patient with acute hypobaropathy developed after a 4-day ascent onto m. Kailas (4800 m) in the Tibet.

Efficient breathing circuit for use at altitude.

We describe a case report of a subject suffering high-altitude cerebral and pulmonary edema successfully treated with low flow rates of supplemental oxygen administered with a breathing system designed to conserve oxygen supplies at high altitude.

Use of the Gamow Bag by EMT-basic park rangers for treatment of high-altitude pulmonary edema and high-altitude cerebral edema.

As part of an emergency medical system protocol, national park service rangers certified at the level of an emergency medical technician-basic (EMT-B) are taught to recognize and treat high-altitude pulmonary edema and high-altitude cerebral edema. In Sequoia and Kings Canyon National Parks, this is done with the assistance of physician on-line medical control as a backup. High-altitude pulmonary edema and high-altitude cerebral edema are both potentially fatal altitude illnesses that can be particularly problematic in the backcountry, where evacuation may be delayed. We report a case of high-altitude pulmonary edema and high-altitude cerebral edema occurring at moderate altitude that was successfully treated by park rangers with the Gamow Bag.

Acute mountain sickness: controversies and advances.

This review discusses the impact of recent publications on pathophysiologic concepts and on practical aspects of acute mountain sickness (AMS). Magnetic resonance imaging studies do not provide evidence of total brain volume increase nor edema within the first 6 to 10 h of exposure to hypoxia despite symptoms of AMS. After 16 to 32 h at about 4500 m, brain volume increases by 0.8% to 2.7%, but morphological changes do not clearly correlate with symptoms of AMS, and lumbar cerebrospinal fluid pressure was unchanged from normoxic values in individuals with AMS. These data do not support the prevailing hypothesis that AMS is caused by cerebral edema and increased intracranial pressure. Direct measurement of increased oxygen radicals in hypoxia and a first study reducing AMS when lowering oxygen radicals by antioxidants suggest that oxidative stress is involved in the pathophysiology of AMS. Placebo-controlled trials demonstrate that theophylline significantly attenuates periodic breathing without improving arterial oxygen saturation during sleep. Its effects on AMS are marginal and clearly inferior to acetazolamide. A most recent large trial with Ginkgo biloba clearly showed that this drug does not prevent AMS in a low-risk setting in which acetazolamide in a low dose of 2 x 125 mg was effective. Therefore, acetazolamide remains the drug of choice for prevention and the recommended dose remains 2 x 250 mg daily until a lower dose has been tested in a high-risk setting and larger clinical trials with antioxidants have been performed.