Severe Acute Mountain Sickness Research Articles

Gastrointestinal syndrome encountered during a train voyage to high altitudes: A 14-day survey of 69 passengers in China

BackgroundThe diagnosis and evaluation of the severity of acute mountain sickness (AMS) continue to be problematic due to a lack of consensus on the inclusion of symptoms in a scoring system. Recent investigations highlight the significance of gastrointestinal symptoms in identifying this condition. However, the specific gastrointestinal symptoms associated with AMS have not been thoroughly elucidated in previous studies, and the underlying risk factors remain inadequately comprehended. MethodsThis study aimed to investigate the characteristics, trends, and risk factors related to gastrointestinal symptoms encountered during train travel to high altitude. A total of 69 passengers, specifically all with medical backgrounds, were surveyed 6 times over a period of 14 days. ResultsThe daily incidence of abdominal discomfort was higher than non-gastrointestinal symptoms within 14 days. Gastrointestinal symptoms demonstrated a greater prevalence, longer duration, and increased risk compared to non-gastrointestinal symptoms, such as headaches. The symptoms of abdominal distension and bowel sound hyperaction were found to be prevalent and persistent among patients diagnosed with AMS, exhibiting a high incidence rate. Gender, age, body mass index (BMI), smoking habits, and alcohol consumption were identified as risk factors associated with the occurrence and duration of gastrointestinal symptoms. ConclusionThis study suggests that gastrointestinal symptoms are more common and persistent when traveling to the plateau by train. These symptoms should be taken into consideration in the further diagnosis and prevention of AMS. Therefore, this study provides a significant theoretical foundation for the prevention and treatment of AMS.

High myopia at high altitudes.

Background: Optic nerve sheath diameter (ONSD) increases significantly at high altitudes, and is associated with the presence and severity of acute mountain sickness (AMS). Exposure to hypobaria, hypoxia, and coldness when hiking also impacts intraocular pressure (IOP). To date, little is known about ocular physiological responses in trekkers with myopia at high altitudes. This study aimed to determine changes in the ONSD and IOP between participants with and without high myopia (HM) during hiking and to test whether these changes could predict symptoms of AMS. Methods: Nine participants with HM and 18 without HM participated in a 3-day trek of Xue Mountain. The ONSD, IOP, and questionnaires were examined before and during the trek of Xue Mountain. Results: The ONSD values increased significantly in both HM (p = 0.005) and non-HM trekkers (p = 0.018) at an altitude of 1,700m. In the HM group, IOP levels were greater than those in the non-HM group (p = 0.034) on the first day of trekking (altitude: 3,150m). No statistically significant difference was observed between the two groups for the values of ONSD. Fractional changes in ONSD at an altitude of 1,700m were related to the development of AMS (r pb = 0.448, p = 0.019) and the presence of headache symptoms (r pb = 0.542, p = 0.004). The area under the ROC curve for the diagnostic performance of ONSD fractional changes at an altitude of 1,700m was 0.859 for predicting the development of AMS and 0.803 for predicting the presence of headache symptoms. Conclusion: Analysis of changes in ONSD at moderate altitude could predict AMS symptoms before an ascent to high altitude. Myopia may impact physiological accommodation at high altitudes, and HM trekkers potentially demonstrate suboptimal regulation of aqueous humor in such environments.

Active ascent accelerates the time course but not the overall incidence and severity of acute mountain sickness at 3,600 m.

Acute mountain sickness (AMS) typically peaks following the first night at high altitude (HA) and resolves over the next 2-3 days, but the impact of active ascent on AMS is debated. To determine the impact of ascent conditions on AMS, 78 healthy Soldiers (means ± SD; age = 26 ± 5 yr) were tested at baseline residence, transported to Taos, NM (2,845 m), hiked (n = 39) or were driven (n = 39) to HA (3,600 m), and stayed for 4 days. AMS-cerebral (AMS-C) factor score was assessed at HA twice on day 1 (HA1), five times on days 2 and 3 (HA2 and HA3), and once on day 4 (HA4). If AMS-C was ≥0.7 at any assessment, individuals were AMS susceptible (AMS+; n = 33); others were nonsusceptible (AMS-; n = 45). Daily peak AMS-C scores were analyzed. Ascent conditions (active vs. passive) did not impact the overall incidence and severity of AMS at HA1-HA4. The AMS+ group, however, demonstrated a higher (P < 0.05) AMS incidence in the active vs. passive ascent cohort on HA1 (93% vs. 56%), similar incidence on HA2 (60% vs. 78%), lower incidence (P < 0.05) on HA3 (33% vs. 67%), and similar incidence on HA4 (13% vs. 28%). The AMS+ group also demonstrated a higher (P < 0.05) AMS severity in the active vs. passive ascent cohort on HA1 (1.35 ± 0.97 vs. 0.90 ± 0.70), similar score on HA2 (1.00 ± 0.97 vs. 1.34 ± 0.70), and lower (P < 0.05) score on HA3 (0.56 ± 0.55 vs. 1.02 ± 0.75) and HA4 (0.32 ± 0.41 vs. 0.60 ± 0.72). Active compared with passive ascent accelerated the time course of AMS with more individuals sick on HA1 and less individuals sick on HA3 and HA4.NEW & NOTEWORTHY This research demonstrated that active ascent accelerated the time course but not overall incidence and severity of acute mountain sickness (AMS) following rapid ascent to 3,600 m in unacclimatized lowlanders. Active ascenders became sicker faster and recovered quicker than passive ascenders, which may be due to differences in body fluid regulation. Findings from this well-controlled large sample-size study suggest that previously reported discrepancies in the literature regarding the impact of exercise on AMS may be related to differences in the timing of AMS measurements between studies.

Progress in the Treatment of High Altitude Cerebral Edema: Targeting REDOX Homeostasis.

With the increasing of altitude activities from low-altitude people, the study of high altitude cerebral edema (HACE) has been revived. HACE is a severe acute mountain sickness associated with exposure to hypobaric hypoxia at high altitude, often characterized by disturbance of consciousness and ataxia. As for the pathogenesis of HACE, previous studies suggested that it might be related to the disorder of cerebral blood flow, the destruction of blood-brain barrier and the injury of brain parenchyma cells caused by inflammatory factors. In recent years, studies have confirmed that the imbalance of REDOX homeostasis is also involved in the pathogenesis of HACE, which mainly leads to abnormal activation of microglia and destruction of tight junction of vascular endothelial cells through the excessive production of mitochondrial-related reactive oxygen species. Therefore, this review summarizes the role of REDOX homeostasis and the potential of the treatment of REDOX homeostasis in HACE, which is of great significance to expand the understanding of the pathogenesis of HACE. Moreover, it will also be helpful to further study the possible therapy of HACE related to the key link of REDOX homeostasis.

Establishing a prediction model of severe acute mountain sickness using machine learning of support vector machine recursive feature elimination

Severe acute mountain sickness (sAMS) can be life-threatening, but little is known about its genetic basis. The study was aimed to explore the genetic susceptibility of sAMS for the purpose of prediction, using microarray data from 112 peripheral blood mononuclear cell (PBMC) samples of 21 subjects, who were exposed to very high altitude (5260 m), low barometric pressure (406 mmHg), and hypobaric hypoxia (VLH) at various timepoints. We found that exposure to VLH activated gene expression in leukocytes, resulting in an inverted CD4/CD8 ratio that interacted with other phenotypic risk factors at the genetic level. A total of 2286 underlying risk genes were input into the support vector machine recursive feature elimination (SVM-RFE) system for machine learning, and a model with satisfactory predictive accuracy and clinical applicability was established for sAMS screening using ten featured genes with significant predictive power. Five featured genes (EPHB3, DIP2B, RHEBL1, GALNT13, and SLC8A2) were identified upstream of hypoxia- and/or inflammation-related pathways mediated by microRNAs as potential biomarkers for sAMS. The established prediction model of sAMS holds promise for clinical application as a genetic screening tool for sAMS.

Can intranasal delivery of dexamethasone facilitate the management of severe altitude disease?

Dexamethasone is the primary treatment for moderate to severe acute mountain sickness and high-altitude cerebral edema. Vomiting or neurologically altered patients require intramuscular or intravenous administration, which requires medical training. Considering the use of the nasal route would expand the possibilities of using dexamethasone in difficult altitude conditions by mountaineers.

AZU1 (HBP/CAP37) and PRKCG (PKC-gamma) may be candidate genes affecting the severity of acute mountain sickness

BackgroundAcute Mountain Sickness (AMS) is one of the diseases that predispose to sudden ascent to high altitudes above 2500 m. Among the many studies on the occurrence and development of AMS, there are few studies on the severity of AMS. Some unidentified phenotypes or genes that determine the severity of AMS may be vital to elucidating the mechanisms of AMS. This study aims to explore the underlying genes or phenotypes associated with AMS severity and to provide evidence for a better understanding of the mechanisms of AMS.MethodsGSE103927 dataset was downloaded from the Gene Expression Omnibus database, and a total of 19 subjects were enrolled in the study. Subjects were divided into a moderate to severe AMS (MS-AMS, 9 subjects) group and a no or mild AMS (NM-AMS, 10 subjects) group based on the Lake Louise score (LLS). Various bioinformatics analyses were used to compare the differences between the two groups. Another dataset, Real-time quantitative PCR (RT-qPCR), and another grouping method were used to validate the analysis results.ResultNo statistically significant differences in phenotypic and clinical data existed between the MS-AMS and NM-AMS groups. Eight differential expression genes are associated with LLS, and their biological functions are related regulating of the apoptotic process and programmed cell death. The ROC curves showed that AZU1 and PRKCG had a better predictive performance for MS-AMS. AZU1 and PRKCG were significantly associated with the severity of AMS. The expression of AZU1 and PRKCG were significantly higher in the MS-AMS group compared to the NM-AMS group. The hypoxic environment promotes the expression of AZU1 and PRKCG. The results of these analyses were validated by an alternative grouping method and RT-qPCR results. AZU1 and PRKCG were enriched in the Neutrophil extracellular trap formation pathway, suggesting the importance of this pathway in influencing the severity of AMS.ConclusionAZU1 and PRKCG may be key genes influencing the severity of acute mountain sickness, and can be used as good diagnostic or predictive indicators of the severity of AMS. Our study provides a new perspective to explore the molecular mechanism of AMS.

Ascent rate and the Lake Louise scoring system: An analysis of one year of emergency ward entries for high-altitude sickness at the Mustang district hospital, Nepal.

More travellers are making swift ascents to higher altitudes without sufficient acclimatization or pharmaceutical prophylaxis as road connectivity develops in the Himalayan region of Nepal. Our study connects ascent rate with prevalence and severity of acute mountain sickness (AMS) among patients admitted to the emergency ward of the Mustang district hospital in Nepal. A register-based, cross-sectional study was conducted between June 2018 and June 2019 to explore associations of Lake Louise scores with ascent profile, sociodemographic characteristics, and comorbidities using chi-square test, t-test, and Bayesian logistic regression. Of 105 patients, incidence of AMS was 74%, of which 61%, 36%, and 3% were mild, moderate, and severe cases, respectively. In the Bayesian-ordered logistic model of AMS severity, ascent rate (odds ratio 3.13) and smoking (odds ratio 0.16) were significant at a 99% credible interval. Based on the model-derived counterfactual, the risk of developing moderate or severe AMS for a middle-aged, non-smoking male traveling from Pokhara to Muktinath (2978m altitude gain) in a single day is twice that of making the ascent in three days. Ascent rate was strongly associated with the likelihood of developing severe AMS among travellers with AMS symptoms visiting Mustang Hospital's Emergency Ward.

Kids With Altitude: Acute Mountain Sickness and Changes in Body Mass and Total Body Water in Children Travelling to 3800 m.

We explored the incidence of acute mountain sickness (AMS) and extravascular lung water (ELW) in children in relation to changes in body composition and peripheral blood oxygenation (SpO2) during 1 week of acclimatization to 3800 m. In a prospective cohort study, 10 children (7 female, ages 7-14 y) and 10 sex-matched adults (ages 23-44 y) traveled via automobile from sea level to 3000 m for 2 nights, followed by 4 nights at 3800 m. Each morning, body mass and body water (bioelectrical impedance), SpO2 (pulse oximetry), AMS (Lake Louise Questionnaire), and ELW (transthoracic echocardiography) were measured. No differences were found between children and adults in SpO2 or ELW. At 3800 m 7 of 10 children were AMS+ vs 4 of 10 adults. Among those AMS+ at 3800 m, the severity was greater in children compared to adults (5±1 vs 3 ± 0; P=0.005). Loss of body mass occurred more quickly in children (day 5 vs day 7) and to a greater extent (-7±3% vs -2±2%; P<0.001); these changes were mediated via a larger relative loss in total body water in children than in adults (-6±5% vs -2±2%; P=0.027). Children demonstrated a higher incidence of AMS than adults, with greater severity among those AMS+. The loss of body water and body mass at high altitude was also greater in children, albeit unrelated to AMS severity. In addition to awareness of AMS, strategies to maintain body weight and hydration in children traveling to high altitudes should be considered.

Acute mountain sickness and sleep disturbances differentially influence cognition and mood during rapid ascent to 3000 and 4050m.

The impact of acute mountain sickness (AMS) and sleep disturbances on mood and cognition at two altitudes relevant to the working and tourist population is unknown. Twenty unacclimatized lowlanders were exposed to either 3000 m (n = 10; 526 mmHg) or 4050 m (n = 10; 460 mmHg) for 20 h in a hypobaric chamber. AMS prevalence and severity was assessed using the Environmental Symptoms Questionnaire (ESQ) and an AMS‐C score ≥ 0.7 indicated sickness. While sleeping for one night both at sea level (SL) and high altitude (HA), a wrist motion detector was used to measure awakenings (Awak, events/h) and sleep efficiency (Eff, %). If Eff was ≥85%, individuals were considered a good sleeper (Sleep+). Mood and cognition were assessed using the Automated Neuropsychological Assessment Metric and Mood Scale (ANAM‐MS). The ESQ and ANAM‐MS were administered in the morning both at SL and after 20 h at HA. AMS severity (mean ± SE; 1.82 ± 0.27 vs. 0.20 ± 0.27), AMS prevalence (90% vs. 10%), depression (0.63 ± 0.23 vs. 0.00 ± 0.24) Awak (15.6 ± 1.6 vs. 10.1 ± 1.6 events/h), and DeSHr (38.5 ± 6.3 vs. 13.3 ± 6.3 events/h) were greater (p < 0.05) and Eff was lower (69.9 ± 5.3% vs. 87.0 ± 5.3%) at 4050 m compared to 3000 m, respectively. AMS presence did not impact cognition but fatigue (2.17 ± 0.37 vs. 0.58 ± 0.39), anger (0.65 ± 0.25 vs. 0.02 ± 0.26), depression (0.63 ± 0.23 vs. 0.00 ± 0.24) and sleepiness (4.8 ± 0.4 vs. 2.7 ± 0.5) were greater (p < 0.05) in the AMS+ group. The Sleep− group, compared to the Sleep+ group, had lower (p < 0.05) working memory scores (50 ± 7 vs. 78 ± 9) assessed by the Sternberg 6‐letter memory task, and lower reaction time fatigue scores (157 ± 17 vs. 221 ± 22), assessed by the repeated reaction time test. Overall, AMS, depression, DeSHr, and Awak were increased (p < 0.05) at 4050 m compared to 3000 m. In addition, AMS presence impacted mood while poor sleep impacted cognition which may deteriorate teamwork and/or increase errors in judgement at HA.

No effect of patent foramen ovale on acute mountain sickness and pulmonary pressure in normobaric hypoxia.

What is the central question to this study? Is there a relationship between a patent foramen ovale and the development of acute mountain sickness and an exaggerated increase in pulmonary pressure in response to 7-10h of normobaric hypoxia? What is the main finding and its importance? Patent foramen ovale presence did not increase susceptibility to acute mountain sickness or result in an exaggerated increase in pulmonary artery systolic pressure with normobaric hypoxia. This suggests hypobaric hypoxia is integral to the increased susceptibility to acute mountain sickness previously reported in those with patent foramen ovale, and patent foramen ovale presence alone does not contribute to the hypoxic pulmonary pressor response. Acute mountain sickness (AMS) develops following rapid ascent to altitude, but its exact causes remain unknown. A patent foramen ovale (PFO) is a right-to-left intracardiac shunt present in ∼30% of the population that has been shown to increase AMS susceptibility with high altitude hypoxia. Additionally, high altitude pulmonary oedema (HAPE) is a severe type of altitude illness characterized by an exaggerated pulmonary pressure response, and there is a greater prevalence of PFO in those with a history of HAPE. However, whether hypoxia per se is causing the increased incidence of AMS in those with a PFO and whether a PFO is associated with an exaggerated increase in pulmonary pressure in those without a history of HAPE is unknown. Participants (n=36) matched for biological sex (18 female) and the presence or absence of a PFO (18 PFO+) were exposed to 7-10h of normobaric hypoxia equivalent to 4755m. Presence and severity of AMS was determined using the Lake Louise AMS scoring system. Pulmonary artery systolic pressure, cardiac output and total pulmonary resistance were measured using ultrasound. We found no significant association of PFO with incidence or severity of AMS and no association of PFO with arterial oxygen saturation. Additionally, there was no effect of a PFO on pulmonary pressure, cardiac output or total pulmonary resistance. These data suggest that hypobaric hypoxia is necessary for those with a PFO to have increased incidence of AMS and that presence of PFO is not associated with an exaggerated pulmonary pressor response.

Older Age as a Predictive Risk Factor for Acute Mountain Sickness

BackgroundOlder populations are increasing and comprise a substantial portion of high-altitude travelers. Aging physiology may influence susceptibility to acute mountain sickness, though prior research remains inconclusive. The goal of this study was to investigate the relationship between increasing age and acute mountain sickness. MethodsThis study was a pooled analysis of 5 prospective randomized controlled trials conducted at White Mountain, California from 2010, 2016-2019 with identical 4-hour rapid ascent from 1242 m to overnight sojourn at 3810 m. Acute mountain sickness was defined by the 2018 Lake Louise Questionnaire criteria. ResultsThere were 491 participants analyzed, 234 (48%) diagnosed with acute mountain sickness and 71 (14%) with moderate acute mountain sickness. Mean age was 37 years (±13). There was no significant correlation between Lake Louise Questionnaire severity and age (r = −0.02; 95% confidence interval [CI], −0.11-0.07, P = .7), 40-year-old dichotomy (t = −0.6; 95% CI, −0.53-0.28, P = .6), or decade of life (P = .4). Logistic regression found no increased odds of acute mountain sickness for increasing age by decade of life (odds ratio [OR] 1.0; 95% CI, 0.97-1.0) or 40-year-old dichotomy (OR 1.4; 95% CI, 0.97-2.1). A history of acute mountain sickness increased odds of acute mountain sickness (OR 3.2; 95% CI, 1.5-7.7). ConclusionsOlder age was not associated with incidence nor severity of acute mountain sickness. A history of altitude illness increased odds of acute mountain sickness and should be used for pre-ascent risk stratification.

MEDEX 2015: Prophylactic Effects of Positive Expiratory Pressure in Trekkers at Very High Altitude.

Purpose: Positive expiratory pressure (PEP) breathing has been shown to increase arterial oxygenation during acute hypoxic exposure but the underlying mechanisms and consequences on symptoms during prolonged high-altitude exposure remain to be elucidated.Methods: Twenty-four males (41 ± 16 years) were investigated, at sea level and at 5,085 m after 18 days of trekking from 570 m. Participants breathed through a face-mask with PEP = 0 cmH2O (PEP0, 0–45th min) and with PEP = 10 cmH2O (PEP10, 46–90th min). Arterial (SpO2), quadriceps and prefrontal (near infrared spectroscopy) oxygenation was measured continuously. Middle cerebral artery blood velocity (MCAv, transcranial Doppler), cardiac function (2D-echocardiography), extravascular lung water accumulation (UsLC, thoracic ultrasound lung comets) and acute mountain sickness (Lake Louise score, LLS) were assessed during PEP0 and PEP10.Results: At 5,085 m with PEP0, SpO2 was 78 ± 4%, UsLC was 8 ± 5 (a.u.) and the LLS was 2.3 ± 1.7 (all P < 0.05 versus sea level). At 5,085 m, PEP10 increased significantly SpO2 (+9 ± 5%), quadriceps (+2 ± 2%) and prefrontal cortex (+2 ± 2%) oxygenation (P < 0.05), and decreased significantly MCAv (−16 ± 14 cm.s–1) and cardiac output (−0.7 ± 1.2 L.min–1) together with a reduced stroke volume (−9 ± 15 mL, all P < 0.05) and no systemic hypotension. PEP10 decreased slightly the number of UsLC (−1.4 ± 2.7, P = 0.04) while the incidence of acute mountain sickness (LLS ≥ 3) fell from 42% with PEP0 to 25% after PEP10 (P = 0.043).Conclusion: PEP10 breathing improved arterial and tissue oxygenation and symptoms of acute mountain sickness after trekking to very high altitude, despite reduced cerebral perfusion and cardiac output. Further studies are required to establish whether PEP-breathing prophylactic mechanisms also occur in participants with more severe acute mountain sickness.

Urinary Metabolites as Predictors of Acute Mountain Sickness Severity.

Individuals sojourning at high altitude (≥2,500m) often develop acute mountain sickness (AMS). However, substantial unexplained inter-individual variability in AMS severity exists. Untargeted metabolomics assays are increasingly used to identify novel biomarkers of susceptibility to illness, and to elucidate biological pathways linking environmental exposures to health outcomes. This study used untargeted nuclear magnetic resonance (NMR)-based metabolomics to identify urine metabolites associated with AMS severity during high altitude sojourn. Following a 21-day stay at sea level (SL; 55m), 17 healthy males were transported to high altitude (HA; 4,300m) for a 22-day sojourn. AMS symptoms measured twice daily during the first 5days at HA were used to dichotomize participants according to AMS severity: moderate/severe AMS (AMS; n=11) or no/mild AMS (NoAMS; n=6). Urine samples collected on SL day 12 and HA days 1 and 18 were analyzed using proton NMR tools and the data were subjected to multivariate analyses. The SL urinary metabolite profiles were significantly different (p≤0.05) between AMS vs. NoAMS individuals prior to high altitude exposure. Differentially expressed metabolites included elevated levels of creatine and acetylcarnitine, and decreased levels of hypoxanthine and taurine in the AMS vs. NoAMS group. In addition, the levels of two amino acid derivatives (4-hydroxyphenylpyruvate and N-methylhistidine) and two unidentified metabolites (doublet peaks at 3.33ppm and a singlet at 8.20ppm) were significantly different between groups at SL. By HA day 18, the differences in urinary metabolites between AMS and NoAMS participants had largely resolved. Pathway analysis of these differentially expressed metabolites indicated that they directly or indirectly play a role in energy metabolism. These observations suggest that alterations in energy metabolism before high altitude exposure may contribute to AMS susceptibility at altitude. If validated in larger cohorts, these markers could inform development of a non-invasive assay to screen individuals for AMS susceptibility prior to high altitude sojourn.

Relationship Between Orthostatic Stress Response And Acute Mountain Sickness Susceptibility At High Altitude: Pilot Study

PURPOSE: To determine whether there is a difference in hemodynamic responses to head-up tilt (HUT) in subjects who do, and do not, experience acute mountain sickness (AMS) during exposure to hypobaric hypoxia. We also aimed to determine if those hemodynamic variables altered during HUT correlated with AMS severity. METHODS: Fifteen participants completed three testing sessions: 1) VO2max test to determine workload at 50% VO2max for hypoxia exposure; 2) HUT test consisted of supine rest for 20 min followed by 70° upright tilt for ≤40 min; and 3) six hours of hypobaric hypoxic exposure simulating 4572 m where participants performed two, 30-min cycling bouts and rested when not exercising. During HUT, continuous blood pressure (BP) monitoring was used to assess systolic and diastolic blood pressure (SBP, DBP); mean arterial pressure (MAP); variability in SBP, DBP, and MAP; and heart rate. AMS scores were reported before and after six hours of hypoxic exposure. Statistical analysis included mixed effects ANOVA to determine changes between supine rest and end of HUT and those who scored a ≥ 3 AMS positive (AMS+) and < 3 AMS negative (AMS-) groups. Correlations by linear regression determined associations between HUT hemodynamic responses and AMS scores. Statistical significance was set to p < 0.05. RESULTS: Systolic, diastolic, and mean arterial blood pressure variability (BPV) increased from supine rest to end of HUT (BPV mean difference ± SD for AMS+ & AMS- groups: SBP = 3.5 ± 3.0, 1.2 ± 1.9: DBP = 1.7 ± 1.5, 0.6 ± 0.9: MAP = 2.8 ± 2.9, 1.1 ± 1.4; p = 0.004, 0.004, & 0.006, respectively). Those with higher AMS scores tended to have a greater magnitude of change in SBP, DBP, and MAP variability during the HUT test (r = 0.65, 0.64, & 0.60, respectively). CONCLUSIONS: Increased BPV indicates BP dysregulation, suggesting that AMS+ individuals may have greater disruptions in BP control that could be observable during a postural change prior to hypoxic exposure. BPV during HUT may be a promising predictive variable for AMS but further research is needed. In the future, researchers should consider using sea-level residents and a range of simulated elevations to determine the predictability of AMS susceptibility by BPV.

Repeated remote ischaemic preconditioning can prevent acute mountain sickness after rapid ascent to a high altitude

ABSTRACT Background This study assessed the effectiveness of 4 different repeated remote ischaemic preconditioning (RIPC) protocols varying in duration and frequency for preventing acute mountain sickness (AMS) after rapid ascent to high altitude. Methods In a randomized but not blinded design, participants were assigned to receive either of the four RIPC treatments at low altitude (Group A, once daily for 1 week; Group B, twice daily for 1 week; Group C, once daily for 4 weeks; and Group D, twice daily for 4 weeks) or control (no specific sham treatment). Participants were then flown to a high altitude (3650 m). The primary outcome was the incidence and severity of AMS evaluated by the Lake Louise score (LLS) after arrival; vital signs were collected simultaneously. Results A total of 250 participants (50 per group; mean age 38.56 ± 0.76 years) were included. The overall AMS incidence was 26.4%. A total of 20 AMS cases (40%) occurred in the control group, 15 cases (30%) both in the RIPC A and RIPC B groups (RR 1.3; 95%CI 0.8-2.3; χ2 = 1.099; p = 0.29), and 8 cases (16%) both in the RIPC C and D groups (RR 2.5; 95%CI 1.2 - 5.2; χ2 = 7.143, p < 0.01), with significantly lower LLSs in the RIPC C and D groups (F = 6.51, p < 0.001). The scores of gastrointestinal symptoms (F = 7.42, p < 0.001) and dizziness (F = 9.82, p < 0.001) but not headache (F = 0.60, p > 0.05) were lower in the RIPC groups compared to control. The blood oxygen saturation level (SpO2) decreased less in the RIPC B, C and D groups compared to control after arrival at a high altitude (F = 11.42, p < 0.001). The number of RIPC treatments received was moderately correlated with SpO2 (R = 0.38, p < 0.001), and SpO2 was moderately inversely correlated with the LLS (R = –0.48, p < 0.001). Conclusion This study demonstrated that a four-week RIPC intervention but not a one-week regimen reduced AMS incidence and severity; however, a placebo effect might have contributed to these results.

Respiratory alkalinization and posterior cerebral artery dilatation predict acute mountain sickness severity during 10h normobaric hypoxia.

What is the central question of this study? The pathophysiology of acute mountain sickness (AMS), involving the respiratory, renal and cerebrovascular systems, remains poorly understood. How do the early adaptations in these systems during a simulated altitude of 5000m relate to AMS risk? What is the main finding and its importance? The rate of blood alkalosis and cerebral artery dilatation predict AMS severity during the first 10 h of exposure to a simulated altitude of 5000m. Slow metabolic compensation by the kidneys of respiratory alkalosis attributable to a brisk breathing response together with excessive brain blood vessel dilatation might be involved in early development of AMS. The complex pathophysiology of acute mountain sickness (AMS) remains poorly understood and is likely to involve maladaptive responses of the respiratory, renal and cerebrovascular systems to hypoxia. Using stepwise linear regression, we tested the hypothesis that exacerbated respiratory alkalosis, as a result of a brisk ventilatory response, sluggish renal compensation in acute hypoxia and dysregulation of cerebral perfusion predict AMS severity. We assessed the Lake Louise score (LLS, an index of AMS severity), fluid balance, ventilation, venous pH, bicarbonate, sodium and creatinine concentrations, body weight, urinary pH and cerebral blood flow [internal carotid artery (ICA) and vertebral artery (VA) blood flow and diameter], in 27 healthy individuals (13 women) throughout 10h exposures to normobaric normoxia (fraction of inspired O2 = 0.21) and normobaric hypoxia (fraction of inspired O2 = 0.117, simulated 5000m) in a randomized, single-blinded manner. In comparison to normoxia, hypoxia increased the LLS, ventilation, venous and urinary pH, and blood flow and diameter in the ICA and VA, while venous concentrations of both bicarbonate and creatinine were decreased (P<0.001 for all). There were significant correlations between AMS severity and the rates of change in blood pH, sodium concentration and VA diameter and more positive fluid balance (P<0.05). Stepwise regression found increased blood pH [beta coefficient (β) = 0.589, P<0.001] and VA diameter (β = 0.418, P = 0.008) to be significant predictors of AMS severity in our cohort [F(2, 20) = 16.1, R2 = 0.617, P<0.001, n = 24], accounting for 62% of the variance in peak LLS. Using classic regression variable selection, our data implicate the degree of respiratory alkalosis and cerebrovascular dilatation in the early stages of AMS development.

Serum neurofilament level increases after ascent to 4559m but is not related to acute mountain sickness.

Background and purposeAt high altitude the brain is exposed to hypoxic stress, which may result in neurological conditions, with acute mountain sickness (AMS) being the most common. We aimed to test the hypothesis that rapid ascent to high altitude alters neuro‐axonal integrity, which can be detected by increased concentration of serum neurofilament light (sNfL) in the blood and may even be exaggerated in people with AMS.MethodsSerum neurofilament light was measured using a single‐molecule array (Simoa, Quanterix, Lexington, MA, USA) assay at low altitude (423 m) in 47 healthy study participants and 44 h after rapid and active ascent to high altitude (4559 m). Peripheral oxygen saturation (SpO2) and partial pressures of oxygen (pO2) were obtained at low and high altitude. The Acute Mountain Sickness‐Cerebral (AMS‐C) scoring system was used to assess AMS incidence and AMS severity.ResultsThere was an increase in sNfL from its baseline value compared with its value at high altitude (6.34 ± 1.96 vs. 7.19 ± 3.14 pg/ml; p = 0.014), but sNfL level did not correlate with SpO2 (r = −0.19; p = 0.066) or pO2 (r = −0.19; p = 0.068). The incidence of AMS at high altitude was 62%. Neither at low altitude (p = 0.706) nor at high altitude (p = 0.985) was there a difference in sNfL between participants with and without AMS as measured 3 days after rapid ascent and 44 h of high‐altitude exposure. Altitude sNfL did not correlate with AMS‐C, either overall or with single‐item scores such as headache severity.ConclusionsRapid ascent of healthy people to high altitude provokes an increase in sNfL 44 h after arrival at 4559 m, which is not related to the magnitude of hypoxemia or AMS incidence and severity, suggesting that neuro‐axonal injury does not directly contribute to AMS.

Low Stroke Volume Index in Healthy Young Men Is Associated with the Incidence of Acute Mountain Sickness after an Ascent by Airplane: A Case-Control Study.

Background The aims of this study were to explore the characteristics of left ventricular (LV) functional changes in subjects with or without acute mountain sickness (AMS) and their associations with AMS incidence. Methods A total of 589 healthy men were enrolled and took a trip from Chengdu (500 m, above sea level (asl)) to Lhasa (3700 m, asl) by airplane. Basic characteristics, physiological data, and echocardiographic parameters were collected both at Chengdu and Lhasa, respectively. AMS was identified by the Lake Louise Questionnaire Score. Results The oxygen saturation (SpO2), end-systolic volume index, end-diastolic volume index (EDVi), stroke volume index (SVi), E-wave velocity, and E/A ratio were decreased, whereas the heart rate (HR), ejection fraction, cardiac index (CI), and A-wave velocity were increased at the third day after arrival, as evaluated by an oximeter and echocardiography. However, AMS patients showed higher HR and lower EDVi, SVi, CI, E-wave velocity, and E/A ratio than AMS-free subjects. Among them, SVi, which is mainly correlated with the changes of EDVi and altered LV filling pattern, was the most valuable factor associated with AMS incidence following receiver-operator characteristic curves and linear and Poisson regression. Compared with subjects in the highest SVi tertile, subjects in the middle SVi tertile showed higher multivariable Incidence Rate Ratios (IRR) for AMS with higher incidences of mild headache and gastrointestinal symptoms, whereas subjects in the lowest SVi tertile showed even higher multivariable IRR with higher incidences of all the symptoms. Conclusions This relatively large-scale case-control study revealed that the reduction of SVi correlated with the altered LV filling pattern was associated with the incidence and clinical severity of AMS.

Altitude, Acute Mountain Sickness, and Acetazolamide: Recommendations for Rapid Ascent.

Toussaint, Claudia M., Robert W. Kenefick, Frank A. Petrassi, Stephen R. Muza, and Nisha Charkoudian. Altitude, acute mountain sickness, and acetazolamide: recommendations for rapid ascent. High Alt Med Biol. 22:5-13, 2021. Background: Sea level natives ascending rapidly to altitudes above 1,500 m often develop acute mountain sickness (AMS), including nausea, headaches, fatigue, and lightheadedness. Acetazolamide (AZ), a carbonic anhydrase inhibitor, is a commonly used medication for the prevention and treatment of AMS. However, there is continued debate about appropriate dosing, particularly when considering rapid and physically demanding ascents to elevations above 3,500 m by emergency medical and military personnel. Aims: Our goal in the present analysis was to evaluate and synthesize the current literature regarding the use of AZ to determine the most effective dosing for prophylaxis and treatment of AMS for rapid ascents to elevations >3,500 m. These circumstances are specifically relevant to military and emergency medical personnel who often need to ascend rapidly and perform physically demanding tasks upon arrival at altitude. Methods: We conducted a literature search from April 2018 to February 2020 using PubMed, Google Scholar, and Web of Science to identify randomized controlled trials that compared AZ with placebo or other treatment with the primary endpoint of AMS incidence and severity. We included only research articles/studies that focused on evaluation of AZ use during rapid ascent. Results: Four doses of AZ (125, 250, 500, and 750 mg daily) were identified as efficacious in decreasing the incidence and/or severity of AMS during rapid ascents, with evidence of enhanced effectiveness with higher doses. Conclusions: For military, emergency medical, or other activities involving rapid ascent to altitudes >3,500 m, doses 500-750 mg/day within 24 hours of altitude exposure appear to be the most effective for minimizing symptoms of AMS.