Severe Acute Mountain Sickness Research Articles

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.

Incidence and Determinants of Acute Mountain Sickness in Mount Kinabalu, Malaysia.

Yang, Su Lan, Nor At'fina Ibrahim, Grazele Jenarun, and Houng Bang Liew. Incidence and determinants of acute mountain sickness in Mount Kinabalu, Malaysia. High Alt Med Biol. 21:265–272, 2020.Background: Acute mountain sickness (AMS) is the most common type of high-altitude sickness. The incidence of AMS varies by mountain location, trail characteristics, and study design. The lack of local epidemiology data has driven us to investigate the incidence and severity of AMS and its associated factors at Mount Kinabalu, Malaysia.Methods: A cohort study was conducted to collect data from climbers after days 1 (3272 m) and 2 (4095 m) of ascent. A self-administered questionnaire was used to explore climbers' demographic and climb characteristics, history of AMS, alcohol exposure, and AMS prevention measures. The Lake Louis score 2018 was used to assess the presence and severity of AMS (cutoff ≥3). Univariate and multivariable logistic regressions were performed to determine the factors associated with the development of AMS on day 2.Results: Data from 345 climbers were analyzed. The incidence of AMS was 23.9% (95% confidence interval [CI] 19.5%–28.7%) and 21.7% (95% CI 17.5%–26.3%) on days 1 and 2, respectively. The majority were mild cases. Experiencing AMS on day 1 (odds ratio [OR] = 12.88; 95% CI 6.71–24.75), alcohol consumption (OR = 3.73; 95% CI 1.66–8.39), receiving guide advice on day 1 (OR = 0.49; 95% CI 0.26–0.93), and age (OR = 0.96; 95% CI 0.93–0.99) were significant determinants of AMS at Mount Kinabalu. Gender, history of AMS, past exposure to high altitude, ascending time, water intake, acetazolamide use, physical fitness, pulse rate, and peripheral capillary oxygen saturation (SpO2) were not associated with AMS at Mount Kinabalu.Conclusion: Future analysis with age strata is required to ascertain the association of age with AMS. Our research has signposted a strong call for collaborative efforts to improve the provision of hiking advice and discourage alcohol sales to mitigate the risk of AMS among Mount Kinabalu climbers.

Mood State Is Related To Acute Mountain Sickness At Both 3000m And 4050m Altitude

PURPOSE: The purpose of this study was to further explicate the relationship between changes in mood states, assessed using the Automated Neuropsychological Assessment Metrics Mood Scale (ANAM-MS), and severity of acute mountain sickness (AMS) without the confounding factors of acetazolamide, climbing rate and environmental conditions. METHODS: Nineteen healthy lowlanders (16 men, 3 women; mean±SE; 22 ±1yr, 76.6 ±3.1 kg, 173.2 ±2.1cm, 46.0 ±1.2 ml · kg−1 · min−1) were randomly exposed to either 3000m (526mmHg) or 4050m (460mmHg) in a hypobaric chamber for 20h. Seven mood states (anger, anxiety, happiness, fatigue, depression, restlessness, and vigor) were assessed using the ANAM-MS; a series of 42 questions answered on a 0-6 Likert Scale. AMS severity was assessed using the AMC-Cerebral Factor Score (AMS-C) of the Environmental Symptoms Questionnaire. Both tests were administered on 8 occasions at sea level (SL), and after 2h and 20h at each altitude (HA2 and HA20). The SL baseline scores for ANAM-MS and AMS-C were calculated as the mean of the 7th (morning) and 8th (afternoon) assessments. RESULTS: There were no differences between altitude groups in mood at SL, HA2 or HA20 so data were combined. There was differences between altitude groups in AMS-C score so data was analyzed separately. No mood state changed significantly from SL to HA2. However, fatigue and restlessness increased (P<0.05) from SL (0.57 ±0.13; 0.07 ±0.03) to HA20 (1.41 ±0.32; 0.52 ±0.20), respectively. In addition, vigor decreased (P<0.05) from SL (1.97 ±0.30) to HA20 (0.88 ±0.21). Happiness, anxiety, depression and anger did not change over time. AMS-C was elevated (P<0.05) at 4050m (1.82 ±0.27) compared to 3000m (0.22 ±0.29) at HA20. Restlessness (r=0.66; P=0.037) and anxiety (r=0.65; P=0.044) correlated with AMS-C at HA20 in the 4050m group. Fatigue (r=0.77; P<0.016) and anger (r=0.95; P=0.0001) correlated with AMS-C at HA20 in the 3000m group. CONCLUSION: ANAM-MS ratings of fatigue, restlessness and decreased vigor emerge as low as 3000m due to hypobaric hypoxia alone. Mood disturbances were related to AMS severity; subjects with the highest ratings of fatigue and anger at 3000m, and restlessness and anxiety at 4050m possessed the highest AMS-C scores in their respective groups. Authors’ views not official U.S. Army or DoD policy. Funding: USAMRDC

Inclusion of resistance routines in a hypoxia training program does not interfere with prevention of acute mountain sickness

ABSTRACT Objectives Acclimatization strategies have been shown to be the best solutions to avoid acute mountain sickness. In this context, we have designed a protocol performed in hypoxia that includes resistance routines in combination with classical endurance training exercises with mountain trekking at mid altitude. Methods Thirty-two volunteers preparing different mountain expeditions participated in the study distributed into two groups. One group trained at 2000 m, while another group trained at 4500–5800 m of simulated altitude in a hypoxic chamber. Acute mountain sickness was monitored by answering the Lake Louise Scale questionnaire during 2 sleeping sessions at 4800 m of simulated altitude at the beginning and at the end of the study. At the same time, oxygen saturation was determined in both groups to monitor physiologic adaptation. Data were also collected from the base camps in each expedition before ascension. Results Acute mountain sickness incidence in the hypoxic group decreased from 100% at the beginning to 12% of individuals at the end of the training period, and it was 25% at the base camps of expeditions. On the other hand, the control group passed from 100% to 88% of individuals at the end of the intervention and 70% at the base camps. At the same time, acute mountain sickness severity was mild in the experimental group compared to moderate-severe in the control group. These data were supported by the oxygen saturation values, indicating adequate adaptation changes for altitude in the hypoxic group. Conclusion The inclusion of resistance workouts in combination with endurance exercises, all performed in hypoxic conditions, does not interfere with an optimal adaptation to altitude and to prevent acute mountain sickness.

Combined methazolamide and theophylline improves oxygen saturation but not exercise performance or altitude illness in acute hypobaric hypoxia.

What is the central question of this study? Does the combination of methazolamide and theophylline reduce symptoms of acute mountain sickness (AMS) and improve aerobic performance in acute hypobaric hypoxia? What is the main finding and its importance? The oral combination of methazolamide (100BID) and theophylline (300BID) improved arterial oxygen saturation but did not reduce symptoms of AMS and impaired aerobic performance. We do not recommend this combination of drugs for prophylaxis against the acute negative effects of hypobaric hypoxia. A limited number of small studies have suggested that methazolamide and theophylline can independently reduce symptoms of acute mountain sickness (AMS) and, if taken together, can improve aerobic exercise performance in normobaric hypoxia. We performed a randomized, double-blind, placebo-controlled, cross-over study to determine if the combination of oral methazolamide and theophylline could provide prophylaxis against AMS and improve aerobic performance in hypobaric hypoxia (∼4875m). Volunteers with histories of AMS were screened at low altitude (1650m) and started combined methazolamide (100mg BID) and theophylline (300mg BID) treatment, or placebo, 72h prior to decompression. Baseline AMS (Lake Louise Questionnaire), blood (haemoglobin, haematocrit), cognitive function, ventilatory and pulse oximetry ( ) measures were assessed at low altitude and repeated between 4 and 10h of exposure to hypobaric hypoxia (PB =425mmHg). Aerobic exercise performance was assessed during a 12.5km cycling time trial (TT) after 4h of hypobaric hypoxia. Subjects repeated all experimental procedures after a 3-week washout period. Differences between drug and placebo trials were evaluated using repeated measures ANOVA (α=0.05). The drugs improved resting by ∼4% (P<0.01), but did not affect the incidence or severity of AMS or cognitive function scores relative to placebo. Subjects' performance on the 12.5km TT was ∼3% worse when taking the drugs (P<0.01). The combination of methazolamide and theophylline in the prescribed dosages is not recommended for use at high altitude as it appears to have no measurable effect on AMS and can impair aerobic performance.

Cardio-respiratory, oxidative stress and acute mountain sickness responses to normobaric and hypobaric hypoxia in prematurely born adults.

We compared the effects of hypobaric and normobaric hypoxia on select cardio-respiratory responses, oxidative stress and acute mountain sickness (AMS) severity in prematurely born individuals, known to exhibit blunted hypoxic ventilatory response. Sixteen prematurely born but otherwise healthy males underwent two 8-h hypoxic exposures under: (1) hypobaric hypoxic [HH; terrestrial altitude 3840m; PiO2:90.2 (0.5) mmHg; BP: 478 (2) mmHg] and (2) normobaric hypoxic [NH; PiO2:90.6 (0.9) mmHg; FiO2:0.142 (0.001)] condition. Resting values of capillary oxyhemoglobin saturation (SpO2), heart rate (HR) and blood pressure were measured before and every 2h during the exposures. Ventilatory responses and middle cerebral artery blood flow velocity (MCAv) were assessed at rest and during submaximal cycling before and at 4 and 8h. Plasmatic levels of selected oxidative stress and antioxidant markers and AMS symptoms were also determined at these time points. HH resulted in significantly lower resting (P = 0.010) and exercise (P = 0.004) SpO2 as compared to NH with no significant differences in the ventilatory parameters, HR or blood pressure. No significant differences between conditions were found in resting or exercising MCAv and measured oxidative stress markers. Significantly lower values of ferric-reducing antioxidant power (P = 0.037) were observed during HH as opposed to NH. AMS severity was higher at 8h compared to baseline (P = 0.002) with no significant differences between conditions. These data suggest that, in prematurely born adults, 8-h exposure to hypobaric, as opposed to normobaric hypoxia, provokes greater reductions in systemic oxygenation and antioxidant capacity. Further studies investigating prolonged hypobaric exposures in this population are warranted. NCT02780908 (ClinicalTrials.gov).

Hypertension and Acute Mountain Sickness in Himalayan Trekkers in Nepal: An Observational Cohort Study

A history of preexisting hypertension is common in people participating in mountain activities; however, the relationship between blood pressure (BP), preexisting hypertension, and acute mountain sickness (AMS) is not well studied. We sought to determine these relationships among trekkers in the Everest region of Nepal. This was a prospective observational cohort study of a convenience sample of adult, nonpregnant volunteers trekking in the Everest Base Camp region in Nepal. We recorded Lake Louise Scores for AMS and measured BP at 2860 m, 3400 m, and 4300 m. The primary outcome was AMS. A total of 672 trekkers (including 60 with history of preexisting hypertension) were enrolled at 2860 m. We retained 529 at 3400 m and 363 at 4300 m. At 3400 m, 11% of participants had AMS, and 13% had AMS at 4300 m. We found no relationship between AMS and measured BP values (P>0.05), nor was there any relation of BP to AMS severity as measured by higher Lake Louise Scores (P>0.05). Preexisting hypertension (odds ratio [OR] 0.16; 95% CI 0.025-0.57), male sex (OR 0.59; 95% CI 0.37-0.96), and increased SpO2 (OR 0.93; 95% CI 0.87-0.98) were associated with reduced rates of AMS in multivariate analyses adjusting for known risk factors for AMS. AMS is common in trekkers in Nepal, even at 3400 m. There is no relationship between measured BP and AMS. However, a medical history of hypertension may be associated with a lower risk of AMS. More work is needed to confirm this novel finding.

Ventilatory Response to Hypoxia and Tolerance to High Altitude in Women: Influence of Menstrual Cycle, Oral Contraception, and Menopause.

Introduction: Tolerance to high altitude in women might be influenced by hormonal status since female hormones modulate ventilation. Methods: Our objectives were (i) to explore in 1060 women, the influence of the phase of menstrual cycle, oral contraception, and menopause with or without hormonal treatment, on hypoxic ventilatory response at exercise (HVRe) and hypoxic cardiac response at exercise (HCRe) measured during a routine hypoxia exercise test, before an exposure to high altitude; (ii) to determine in 260 women exposed to high altitude, the influence of menopause and oral contraceptive and other drug use, on the prevalence of severe acute mountain sickness (sAMS). Four groups were defined: premenopausal with or without oral contraception and postmenopausal with or without hormonal treatment. Results: In premenopausal women without contraception, HVRe was higher in the early luteal/midluteal phase than in the early follicular phase (0.89 ± 0.37 vs. 0.75 ± 0.27 mL/[min · kg], p = 0.03). HVRe was similar in postmenopausal versus premenopausal women. HCRe was lower in postmenopausal women (p < 0.001), due to aging. HVRe decreased from second to fourth decade of age and increased from fourth to eighth decade, while HCRe consistently decreased with aging. Oral contraception or hormonal treatment had no effect on responses to hypoxia. The prevalence of sAMS was similar in all groups. Severe high-altitude illness score was higher and HVRe lower in women with sAMS. Conclusion: (i) physiological responses to hypoxic exercise depend on the ovarian cycle phase and menopause status, (ii) oral contraception and hormonal treatment have no influence on the tolerance to high altitude, and (iii) independent of hormonal status, aging modulates physiological responses to hypoxia.

Interstitial Pulmonary Edema Assessed by Lung Ultrasound on Ascent to High Altitude and Slight Association with Acute Mountain Sickness: A Prospective Observational Study.

Background: Acute mountain sickness (AMS) is a common disease that may have a pulmonary component, as suggested by interstitial pulmonary edema quantified by the B-line score (BLS) on ultrasound (US). This subclinical pulmonary edema has been shown to increase with ascent to high altitude and AMS severity, but has not been prospectively associated with AMS incidence in a large prospective study. Materials and Methods: This prospective observational study was part of a randomized controlled trial enrolling healthy adults over four weekends ascending White Mountain, California. Subjects were assessed by lung US and the Lake Louise Questionnaire at 4110 ft (1240 m), upon ascent to 12,500 ft (3810 m), and the next morning at 12,500 ft (3810 m). Results: Three hundred five USs in total were completed on 103 participants, with 73% total incidence of AMS. The mean (±standard deviation) BLS increased from baseline (1.15 ± 1.80) to high altitude (2.56 ± 2.86), a difference of 1.37 (±2.48) (p = 0.04). Overall BLS was found, on average, to be higher among those diagnosed with AMS than without (2.97 vs. 2.0, p = 0.04, 95% confidence interval [CI] -∞ to -0.04). The change in BLS (ΔBLS) from low altitude baseline was significantly associated with AMS (0.88 vs. 1.72, r2 = 0.023, 95% CI -∞ to -0.01, p = 0.048). Conclusions: Interstitial subclinical pulmonary edema by lung US was found to have a small but significant association with AMS.

Reduced Acetazolamide Dosing in Countering Altitude Illness: A Comparison of 62.5 vs 125 mg (the RADICAL Trial)

North American guidelines propose 125 mg acetazolamide twice daily as the recommended prophylactic dose to prevent acute mountain sickness (AMS). To our knowledge, a dose lower than 125 mg twice daily has not been studied. We conducted a prospective, double-blind, randomized, noninferiority trial of trekkers to Everest Base Camp in Nepal. Participants received the reduced dose of 62.5 mg twice daily or the standard dose of 125 mg twice daily. Primary outcome was incidence of AMS, and secondary outcomes were severity of AMS and side effects in each group. Seventy-three participants had sufficient data to be included in the analysis. Overall incidence of AMS was 21 of 38 (55.3%) in reduced-dose and 21 of 35 (60.0%) in standard-dose recipients. The daily incidence rate of AMS was 6.7% (95% CI 2.5-10.9) for each individual in the reduced-dose group and 8.9% (95% CI 4.5-13.3) in the standard-dose group. Overall severity of participants' Lake Louise Score was 1.014 in the reduced-dose group and 0.966 in the standard-dose group (95% CI 0.885-1.144). Side effects were similar between the groups. The reduced dose of acetazolamide at 62.5 mg twice daily was noninferior to the currently recommended dose of 125 mg twice daily for the prevention of AMS. Low incidence of AMS in the study population may have limited the ability to differentiate the treatment effects. Further research with more participants with greater rates of AMS would further elucidate this reduced dosage for preventing altitude illness.

Associations between the gut microbiota and host responses to high altitude.

Hypobaric hypoxia and dietary protein and fat intakes have been independently associated with an altered gastrointestinal (GI) environment and gut microbiota, but little is known regarding host-gut microbiota interactions at high altitude (HA) and the impact of diet macronutrient composition. This study aimed to determine the effect of dietary protein:fat ratio manipulation on the gut microbiota and GI barrier function during weight loss at high altitude (HA) and to identify associations between the gut microbiota and host responses to HA. Following sea-level (SL) testing, 17 healthy males were transported to HA (4,300 m) and randomly assigned to consume provided standard protein (SP; 1.1 g·kg−1·day−1, 39% fat) or higher protein (HP; 2.1 g·kg−1·day−1, 23% fat) carbohydrate-matched hypocaloric diets for 22 days. Fecal microbiota composition and metabolites, GI barrier function, GI symptoms, and acute mountain sickness (AMS) severity were measured. Macronutrient intake did not impact fecal microbiota composition, had only transient effects on microbiota metabolites, and had no effect on increases in small intestinal permeability, GI symptoms, and inflammation observed at HA. AMS severity was also unaffected by diet but in exploratory analyses was associated with higher SL-relative abundance of Prevotella, a known driver of interindividual variability in human gut microbiota composition, and greater microbiota diversity after AMS onset. Findings suggest that the gut microbiota may contribute to variability in host responses to HA independent of the dietary protein:fat ratio but should be considered preliminary and hypothesis generating due to the small sample size and exploratory nature of analyses associating the fecal microbiota and host responses to HA.NEW & NOTEWORTHY This study is the first to examine interactions among diet, the gut microbiota, and host responses to weight loss at high altitude (HA). Observed associations among the gut microbiota, weight loss at HA, and acute mountain sickness provide evidence that the microbiota may contribute to variability in host responses to HA. In contrast, dietary protein:fat ratio had only minimal, transient effects on gut microbiota composition and bacterial metabolites which were likely not of clinical consequence.

The Smell of Hypoxia: using an electronic nose at altitude and proof of concept of its role in the prediction and diagnosis of acute mountain sickness.

† Electronic nose (e‐nose) devices may be used to identify volatile organic compounds (VOCs) in exhaled breath. VOCs generated via metabolic processes are candidate biomarkers of (patho)physiological pathways. We explored the feasibility of using an e‐nose to generate human “breathprints” at high altitude. Furthermore, we explored the hypothesis that pathophysiological processes involved in the development of acute mountain sickness (AMS) would manifest as altered VOC profiles. Breath analysis was performed on Sherpa and lowlander trekkers at high altitude (3500 m). The Lake Louise Scoring (LLS) system was used to diagnose AMS. Raw data were reduced by principal component (PC) analysis (PCA). Cross validated linear discriminant analysis (CV‐LDA) and receiver‐operating characteristic area under curve (ROC‐AUC) assessed discriminative function. Breathprints suitable for analysis were obtained from 58% (37/64) of samples. PCA showed significant differences between breathprints from participants with, and without, AMS; CV‐LDA showed correct classification of 83.8%, ROC‐AUC 0.86; PC 1 correlated with AMS severity. There were significant differences between breathprints of participants who remained AMS negative and those whom later developed AMS (CV‐LDA 68.8%, ROC‐AUC 0.76). PCA demonstrated discrimination between Sherpas and lowlanders (CV‐LDA 89.2%, ROC‐AUC 0.936). This study demonstrated the feasibility of breath analysis for VOCs using an e‐nose at high altitude. Furthermore, it provided proof‐of‐concept data supporting e‐nose utility as an objective tool in the prediction and diagnosis of AMS. E‐nose technology may have substantial utility both in altitude medicine and under other circumstances where (mal)adaptation to hypoxia may be important (e.g., critically ill patients).

Characteristics of Headache and Relationship to Acute Mountain Sickness at 4559 Meters

The goals of this study were to characterize headache at high altitude in relation to the severity of acute mountain sickness (AMS), to investigate whether a history of migraine or nonmigrainous headache at low altitude is a risk factor for AMS and to estimate its effect size in relation to established major risk factors. We performed a secondary, extended analysis of data obtained from 1320 mountaineers staying overnight at the Capanna Margherita (4559 m). Headache at low and high altitude was classified according to the criteria of the International Headache Society. About 45% of the mountaineers suffered from headache in the evening of the arrival day at 4559 m. In those with headache, tension type headache decreased from 62% to 29% and 13% with no AMS (AMS-C <0.70), moderate AMS, and more severe AMS (AMS-C ≥1.5), while headache fulfilling the criteria of migraine increased correspondingly from 14% to 34% and 69%. A history of migraine or any type of headache at low altitude is a minor predictor of AMS that does not significantly contribute to AMS risk in a multivariate analysis including the major risk factors such as history of AMS, rate of ascent, and degree of preacclimatization in this population of alpine mountaineers. The association between more severe AMS and migrainous headache may be due to common nonspecific symptoms but a common underlying pathophysiology of AMS and migraine cannot be excluded. Despite this association a history of migraine or other headache at low altitude is not a major risk factor for AMS.

Effect of Intermittent Normobaric Hypoxia Exposures on Acute Mountain Sickness During Acute Ascent to 3500 m in Indian Military Personnel

&lt;p&gt;In emergencies/war like situations, rapid deployment of army personnel into high altitude occurs without proper acclimatization. Rapid deployment of unacclimatized soldiers to high mountainous environments may cause debilitating effects on operational capabilities and development of acute mountain sickness (AMS). Altitude acclimatization is the best strategy for the prevention of AMS Use of pharmacological intervention for prevention of AMS is a common practice. The use of intermittent hypoxic exposure (IHE) is an alternative approach for altitude acclimatization and it reduces occurrence and severity of AMS is. But, the use of intermittent normobaric hypoxia exposure at sea level on occurrence of AMS after acute ascent to 3500m altitude in Indian army personnel has not been tested yet.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;

Systemic blood pressure at exercise in hypoxia in hypertensive and normotensive patients.

The current study aimed to determine whether acute hypoxia exposure in laboratory conditions associated with exercise induces an increase in systemic blood pressure (BP) in normotensive and hypertensive patients, and whether hypertensive patients are more prone to develop severe acute mountain sickness (sAMS). Finally, to determine if BP changes at exercise in acute hypoxia in hypertensive patients are predictive factors for sAMS. From 2012 to 2015, 852 normotensive and 106 hypertensive patients went through an acute hypoxia exercise test before a sojourn at high altitude. A subgroup of 228 normotensive was selected to match age, sex ratio, body weight and BMI and compared with the hypertensive group. In normotensive and hypertensive patients, for a given workload, BP was higher in hypoxia than in normoxia, whereas, for a given heart rate, it was lower in hypoxia than in normoxia. Hypertensive patients treated by beta-blockers showed lower arterial oxygen saturation (vs. other treatments) and blunted cardiac and ventilatory responses to hypoxia at exercise. Based on questionnaires filled out at high altitude, hypertensive patients were not more prone than normotensive patients to develop sAMS. During the laboratory acute hypoxic exercise test, hypertensive patients suffering from sAMS, although taking acetazolamide showed similar BP than hypertensive patients without sAMS and without acetazolamide. We hypothesize that acute hypoxia with exercise in laboratory conditions induces a peripheral vasodilation that balances vasoconstriction and tachycardia centrally induced through the adrenergic system. Hypertensive and normotensive patients behave similarly during exercise in acute hypoxia. Acute hypoxia does not exacerbate the exercise-induced increase in BP. BP variation, during the acute hypoxia exercise test, is not a useful predictor of intolerance to high altitude. Based on laboratory tests in acute hypoxia, hypertensive patients may not be at higher risk to develop sAMS at high altitude.

Incidence and severity of acute mountain sickness and associated symptoms in children trekking on Xue Mountain, Taiwan.

BackgroundAcute mountain sickness (AMS) occurs in non-acclimatized people after an acute ascent to an altitude of 2,500 m or higher. The aim of this study was to examine the incidence and severity of AMS and associated symptoms in children.MethodsThe prospective observational study included 197 healthy, non-acclimatized 11 and 12-year-old children trekking the round-trip from the trailhead to the summit of Xue Mountain, Taiwan (2,179 m to 3,886 m) over 3 days. AMS was evaluated at Qika Hut (2,460 m) on Day 1, at Sanliujiu Hut on Day 2 (3,100 m), and at the same altitude (3,100 m) after reaching the summit on Day 3. We used the Lake Louise Score (LLS) to diagnose AMS and record daily AMS-associated symptoms. We gave acetazolamide to children with mild to moderate AMS. Dexamethasone was reserved for individuals suffering from severe AMS. Acetaminophen was administrated to children with headache, and metoclopramide for those with nausea or vomiting.ResultsThere were 197 subjects eligible for analysis. The overall incidence of AMS was 40.6%, which was higher in males and in subjects with a higher body mass index (BMI) (p < 0.05). The prevalence of AMS on Day 1 was 5.6%, which was significantly lower than that on Day 2 (29.4%) and Day 3 (23.4%). The mean LLS of all subjects was 1.77 ± 2.08. The overall incidence of severe AMS (LLS ≥ 5) was 12.5%. The mean LLS of the AMS group (3.02 ± 2.46) was significantly higher than that of the non-AMS group (0.92 ± 1.16, p < 0.001). Among the AMS group, the mean LLS was 1.00 ± 1.55 on Day 1, 4.09 ± 1.97 on Day 2, and 3.98 ± 2.42 on Day 3. The most common symptom was sleep disturbance followed by dizziness, and headache. The prevalence of headache was 46.2% on Day 2 at 3,100 m, and 31.3% on Day 3 at the same altitude after climbing the summit (3,886 m). Males experienced significantly more headache and fatigue than females (p < 0.05). The LLS and prevalence of all AMS symptoms were significantly higher in the AMS than the non-AMS group (p < 0.05).ConclusionsThe AMS incidence among children trekking to Xue Mountain was 40.6%. AMS is common and mostly manifests as mild symptoms. Gender (male) and a higher BMI could be considered two independent risk factors of higher AMS incidence. Sleep disturbance is the most common symptom, and the lower prevalence of headache on Day 3 may be due to the effects of medication and/or acclimatization.

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.

Budesonide Versus Acetazolamide for Prevention of Acute Mountain Sickness

BackgroundInhaled budesonide has been suggested as a novel prevention for acute mountain sickness. However, efficacy has not been compared with the standard acute mountain sickness prevention medication acetazolamide. MethodsThis double-blind, randomized, placebo-controlled trial compared inhaled budesonide versus oral acetazolamide versus placebo, starting the morning of ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (headache and Lake Louise Questionnaire ≥3 and another symptom). ResultsA total of 103 participants were enrolled and completed the study; 33 (32%) received budesonide, 35 (34%) acetazolamide, and 35 (34%) placebo. Demographics were not different between the groups (P > .09). Acute mountain sickness prevalence was 73%, with severe acute mountain sickness of 47%. Fewer participants in the acetazolamide group (n = 15, 43%) developed acute mountain sickness compared with both budesonide (n = 24, 73%) (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.3-10.1) and placebo (n = 22, 63%) (OR 0.5, 95% CI 0.2-1.2). Severe acute mountain sickness was reduced with acetazolamide (n = 11, 31%) compared with both budesonide (n = 18, 55%) (OR 2.6, 95% CI 1-7.2) and placebo (n = 19, 54%) (OR 0.4, 95% CI 0.1-1), with a number needed to treat of 4. ConclusionBudesonide was ineffective for the prevention of acute mountain sickness, and acetazolamide was preventive of severe acute mountain sickness taken just before rapid ascent.

Findings of Cognitive Impairment at High Altitude: Relationships to Acetazolamide Use and Acute Mountain Sickness.

Acute mountain sickness (AMS) is defined by patient-reported symptoms using the Lake Louise Score (LLS), which provides limited insight into any possible underlying central nervous system (CNS) dysfunction. Some evidence suggests AMS might coexist with altered neural functioning. Cognitive impairment (CI) may go undetected unless a sensitive test is applied. Our hypothesis was that a standardized test for mild CI would provide an objective measure of CNS dysfunction, which may correlate with the symptoms of AMS and so provide a potential new tool to better characterize altitude-related CNS dysfunction. We compared a cognitive screening tool with the LLS to see if it correlated with CNS dysfunction. Adult native English-speaking subjects visiting Himalayan Rescue Association aid stations in Nepal at 3520 m (11,548 ft) and 4550 m (14,927 ft) were recruited. Subjects were administered the LLS and a slightly modified version of the environmental Quick mild cognitive impairment screen (eQmci). Medication use for altitude illness was recorded. Scores were compared using the Spearman's correlation coefficient. Data also included medication use. Seventy-nine subjects were enrolled. A cut-off of three or greater was used for the LLS to diagnose AMS and 67 or less for the eQmci to diagnose CI. There were 22 (28%) subjects who met criteria for AMS and 17 (22%) subjects who met criteria for CI. There was a weak correlation (r2 = 0.06, p = 0.04) between eQmci score and LLS. In matched subjects with identical LLS, recent acetazolamide use was associated with significantly more CI. Field assessment of CI using a rapid standardized tool demonstrated that a substantial number of subjects were found to have mild CI following rapid ascent to 3520-4550 m (11,548-14,927 ft). The weak correlation between the LLS and eQmci suggests that AMS does not result in CI. Use of acetazolamide appears to be associated with CI at all levels of AMS severity.

Oxidative Stress in Acute Hypobaric Hypoxia.

Irarrázaval, Sebastián, Claudio Allard, Juan Campodónico, Druso Pérez, Pablo Strobel, Luis Vásquez, Inés Urquiaga, Guadalupe Echeverría, and Federico Leighton. Oxidative stress in acute hypobaric hypoxia. High Alt Med Biol. 18:128-134, 2017.-The effects of acute hypobaric hypoxia endured by mountaineers were studied, specifically as evidenced by acute mountain sickness (AMS) and oxidative stress damage. Ten male volunteers were exposed to acute hypobaric hypoxia, and AMS was evaluated through arterial oxygen saturation (SaO2), cardiac rate, and the Lake Louise Score (LLS). Oxidative stress was determined through blood profile tests performed 24 hours before and after high-altitude exposure, assessing the oxidative damage and antioxidant profiles. Dietary habits were assessed using the Chilean Mediterranean Diet Index. During ascent (i.e., first 8 hours), all volunteers presented AMS (LLS ≥3 points), as manifested by a median LLS increment of four points, a 15 bpm cardiac rate, and 17% decrease in SaO2. Additionally, plasma lipid oxidative damage increased after the expedition, as evaluated through malondialdehyde, which was directly correlated with the LLS (R2 = 0.720, p = 0.003) and inversely correlated with SaO2 (R2 = 0.436; p = 0.035) at a high altitude. Preascent carbonyl levels were inversely correlated to SaO2 (R2 = 0.490; p = 0.008) and directly correlated to cardiac rate (R2 = 0.225, p = 0.016) at a high altitude. Moreover, dietary habits were inversely correlated with increased carbonyls during the expedition (R2 = 0.436; p = 0.047). In conclusion, acute hypobaric hypoxia induced AMS and an increment in oxidative stress markers 24 hours after altitude exposure in the volunteers. Furthermore, oxidative stress damage was related to AMS severity. Finally, volunteers with closer adherence to a Mediterranean diet presented a lower increase in oxidative damage during ascent, reflecting the potential preventive role of diet against AMS.