Incidence Of Acute Mountain Sickness Research Articles

Intermittent hypoxia exposure at sea level improves functional capacity (6MWT) at high altitude

Objectives: Our primary objective is to observe whether acclimatisation is elicited by the intermittent hypoxic exposure (IHE) protocol. For this, we have utilised performance in a 6-min walk test (6MWT) as a tool to assess physiological responses to high altitude (HA) both in control and IHE-exposed groups, respectively. Materials and Methods: The study was a prospective cohort study conducted on Indian army volunteers (n = 57) and they were divided into two groups, a control group (CG) and an experimental group (EG). At the sea level, a baseline study was carried out on barometric pressure. IHE was performed at sea level in the normobaric hypoxia chamber (low fraction of inspired oxygen [FiO2], at normal barometric pressure, 740 mmHg), in which the FiO2 of the chamber was artificially decreased using O2-filtering membranes. The oxygen percentage was constantly maintained at 12%-13%. After recording the baseline, the subjects were exposed to a normobaric hypoxia chamber at 12%-13% FiO2 (altitude – equivalent to 4350 m Approx). Heart rate and blood pressure (BP) were recorded with a battery-operated portable BP monitor (OMRON) at both locations. A finger pulse oximeter probe was set on the right index finger to measure the resting oxygen saturation (SpO2) level (Model MU 300). Incidence of acute mountain sickness (AMS) was scored with the help of the standard Lake Louise questionnaire (LLS). Total LLS scores more than >3 (range 0–15) were considered AMS. Results: EG individuals that went through IHE performed better at 6MWT at Stage I (P = 0.03). EG also had better SpO2, levels as compared to CG (P = 0.00) at Stage II (P = 0.03). Furthermore, there was a significant difference in the Borg’s Scale between CG and EG. The Delta SpO2 of EG was better as compared to CG in all stages, albeit not significant (P = 0.07). There was a significant difference between IHE and CG groups, and CG was at an increased risk for lower SpO2 (8.00 [1.21–52.60], P = 0.03). Conclusion: The findings elucidate the benefits of IHE in rapid acclimatisation, and it contributed to better distance covered as shown by 6MWT as well and reduces hypoxic incidents in HA.

Poor Knowledge of Acute Mountain Sickness in Latin American Medical Students.

Acute altitude exposure is a common event in Latin America that can result in mild to severe altitude illness. Medical students from some Latin American countries receive little information on this topic. Our aim was to determine the knowledge and incidence of acute mountain sickness (AMS), as well as the methods used to prevent AMS among medical students attending the Pan-American Student Meeting in Cusco, Peru, a city at high altitude (3400 m). We conducted a cross-sectional study on medical students attending a conference. Participants completed a questionnaire on the day of registration that collected demographic data and investigated students' knowledge of AMS, its prophylaxis, and their personal experience of symptoms. A total of 840 students attended the meeting. Two hundred eighty-eight returned surveys, 51 from high altitude locations. Respondent age was 23±3 y (mean±SD), and 72% were female. Thirty-two percent had basic knowledge about symptoms of AMS. Headache was recognized as a symptom by 79%. Knowledge of AMS prophylaxis was reported by 70%. Coca leaf products and dimenhydrinate were mentioned by 30 and 16%, respectively, whereas acetazolamide was recognized by only 10% of participants. AMS incidence was 42%. Prophylactic measures were adopted by 47% of the participants in our study. Thirty-six percent used dimenhydrinate and 27% used coca tea. Less than 1% used acetazolamide as recommended. We found poor knowledge of AMS and effective prophylaxis among medical students from several South American countries traveling to 3400 m.

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.

The Impact of Nocebo and Placebo Effects on Reported Incidence of Acute Mountain Sickness.

Bärtsch Peter. The impact of nocebo and placebo effects on reported incidence of acute mountain sickness. High Alt Med Biol. 23:8-17, 2022.-Well comparable studies reporting acute mountain sickness (AMS) in nonacclimatized, acutely exposed individuals performed at 3,450-3,650 m (9 studies) and 4,559-4,675 m (18 studies) at real altitude or in hypobaric or in normobaric hypoxic chambers were analyzed with the hypothesis that the study design impacts occurrence of AMS. Individual symptoms and overall scores of AMS were not different between the three modalities of exposure to a comparable degree of hypoxia, indicating that hypobaria has, if at all, minimal influence on AMS. Studies not focusing versus those focusing on AMS report lower scores and prevalence of AMS at 3,500 m, but not at 4,559 m, while frequent assessment may be associated with more severe AMS. These data suggest that focusing on AMS creates expectations of getting AMS (nocebo effects) and increases its prevalence, while not paying attention reduces negative expectations and thus AMS. On the other hand, interventions promising improvement may cause positive expectations (placebo effect). Information about purpose and dangers of a study, repeated assessments for AMS, previous experiences of AMS, and observation of illness in other study participants are major factors contributing to negative expectations and thus nocebo effects increasing AMS. They should be considered when designing studies and subject information and be reported in detail in publications of studies on AMS.

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.

Echocardiographic Right Ventricular Outflow Track Notch Formation and the Incidence of Acute Mountain Sickness.

Yuan, Fangzhengyuan, Zhexue Qin, Chuan Liu, Shiyong Yu, Jie Yang, Jun Jin, Shizhu Bian, Xubin Gao, Jihang Zhang, Chen Zhang, Mingdong Hu, Jingbin Ke, Yuanqi Yang, Jingdu Tian, Chunyan He, Wenzhu Gu, Chun Li, Rongsheng Rao, and Lan Huang. Echocardiographic right ventricular outflow track notch formation and the incidence of acute mountain sickness. High Alt Med Biol. 22:263-273, 2021. Background: High-altitude exposure causes acute mountain sickness (AMS) and increases pulmonary arterial pressure (PAP). The notching of echocardiographic right ventricular outflow tract flow velocity envelope (right ventricular outflow tract [RVOT] notching), is related to increased PAP. We speculate that acute high-altitude exposure may trigger RVOT notching, which may be associated with AMS. Methods: All 130 subjects, ascended to 4,100 m from low altitude by bus within 7 days, underwent physiological and echocardiographic testing. The subjects with a total score of 3 or above and in the presence of a headache were diagnosed with AMS according to Lake Louise criteria. Results: After high-altitude exposure, the incidence of RVOT notching and AMS was 20% and 28.5%, respectively. The subjects with AMS had a higher incidence (37.8%) of RVOT notching than those without AMS (12.9%). Multivariate logistic regression analysis showed that RVOT notching was associated with systolic pulmonary artery pressure (SPAP) (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.05-1.17; p < 0.001) and the occurrence of AMS (OR, 5.48; 95% CI, 1.96-15.35; p = 0.001). Although linear regression analysis showed a weak correlation between SPAP and Lake Louise AMS score in the overall population (r = 0.20, p = 0.020), this correlation was more pronounced in the subpopulation with RVOT notching (r = 0.44, p = 0.023) and SPAP was not related to Lake Louise AMS score in the subpopulation without RVOT notching (r = 0.03, p = 0.698). Among AMS symptoms, the incidence of headache and fatigue were higher in subjects with RVOT notching than those in subjects without RVOT notching. Conclusions: We first observe that high-altitude exposure triggers RVOT notching formation, which is associated with AMS occurrence. Clinical Trials.gov ID: ChiCTR-RCS-12002232.

Rapid Acclimatisation to High Altitude by Intermittent Hypoxia Training at Sea Level Role of Biochemical Markers

Rapid induction of soldiers to high altitude under emergency situation may lead to higher incidence of acute mountain sickness (AMS) and other high altitude illness. Intermittent Hypoxia Training (IHT) at sea level before going to high altitude is an approach for rapid acclimatisation. This approach may be helpful to reduce the occurrence of AMS and leads to better acclimatisation at high altitude in shorter duration. The present study evaluates the role of biochemical markers of acclimatisation after IHT before induction to actual high altitude. The study participants were Indian Army Personnel (n=30) and they were divided into two groups of control (n=16) and IHT exposed (n=14). The intermittent hypoxia training was administered at 12 per cent Oxygen for 4h/day for 4 days at sea level using normobaric hypoxia chamber and within 24 hrs - 48 hrs the subjects were airlifted to Leh, Ladakh, India at 11,700 ft. Preconditioning with IHT may be beneficial in maintaining antioxidant levels and ameliorate oxidative stress at high altitude. The hypoxia responsive proteins like Hemeoxygenase -1 (HO-1) and Vascular endothelial growth factor (VEGF) and the cytoprotective stress proteins, which facilitate the acclimatisation, may also get benefited by IHT exposure.

Physiological responses during ascent to high altitude and the incidence of acute mountain sickness.

Acute mountain sickness (AMS) occurs when there is failure of acclimatisation to high altitude. The aim of this study was to describe the relationship between physiological variables and the incidence of AMS during ascent to 5300 m. A total of 332 lowland‐dwelling volunteers followed an identical ascent profile on staggered treks. Self‐reported symptoms of AMS were recorded daily using the Lake Louise score (mild 3–4; moderate‐severe ≥5), alongside measurements of physiological variables (heart rate, respiratory rate (RR), peripheral oxygen saturation (SpO2) and blood pressure) before and after a standardised Xtreme Everest Step‐Test (XEST). The overall occurrence of AMS among participants was 73.5% (23.2% mild, 50.3% moderate–severe). There was no difference in gender, age, previous AMS, weight or body mass index between participants who developed AMS and those who did not. Participants who had not previously ascended >5000 m were more likely to get moderate‐to‐severe AMS. Participants who suffered moderate‐to‐severe AMS had a lower resting SpO2 at 3500 m (88.5 vs. 89.6%, p = 0.02), while participants who suffered mild or moderate‐to‐severe AMS had a lower end‐exercise SpO2 at 3500 m (82.2 vs. 83.8%, p = 0.027; 81.5 vs. 83.8%, p < 0.001 respectively). Participants who experienced mild AMS had lower end‐exercise RR at 3500 m (19.2 vs. 21.3, p = 0.017). In a multi‐variable regression model, only lower end‐exercise SpO2 (OR 0.870, p < 0.001) and no previous exposure to altitude >5000 m (OR 2.740, p‐value 0.003) predicted the development of moderate‐to‐severe AMS. The Xtreme Everest Step‐Test offers a simple, reproducible field test to help predict AMS, albeit with relatively limited predictive precision.

Abstract 14359: Single Nucleotide Polymorphisms in Genes Involved in L-arginine / Dimethylarginine Metabolism Predispose for Pulmonary Hypertension and Acute Mountain Sickness at High Altitude

Introduction: Chronic (CH) and chronic-intermittent (CIH) exposure to hypoxia at high altitude causes acute or chronic mountain sickness and elevation of mean pulmonary arterial pressure (mPAP). This is paralleled by increased plasma levels of ADMA, an endogenous inhibitor of NO synthesis. ADMA is cleaved by dimethylarginine dimethylaminohydrolase (DDAH1 and DDAH2), whilst symmetric dimethylarginine (SDMA) is cleaved by AGXT2. Arginase (ARG1 and ARG2) competes with endothelial NO synthase (NOS3) for L-arginine as substrate. We have shown previously that baseline ADMA (at sea level) determines mPAP after six months of CIH; cut-off values of 25 mm Hg and 30 mm Hg are being used to diagnose high altitude pulmonary hypertension. Hypothesis: We hypothesized that genetic variability in genes coding for core enzymes of ADMA, SDMA, and L-arginine metabolism may predispose individuals for high altitude disease and pulmonary hypertension. Methods: We genotyped 16 common single nucleotide polymorphisms in the NOS3, DDAH1, DDAH2, AGXT2, ARG1 and ARG2 genes of 69 healthy male Chilean subjects. Study participants adhered to a CIH regimen (5d at 3,550m, 2d at sea level) for six months. Metabolites were measured by LC-MS/MS; mPAP was estimated by echocardiography at six months, and altitude acclimatization was assessed by Lake Louise Score and arterial oxygen saturation. Results: Carriers of the minor allele of DDAH1 rs233112 had a higher mean baseline ADMA level (0.76±0.03 vs. 0.67±0.02 μmol/l; p&lt;0.05), whilst the major allele of DDAH2 rs805304 was linked to an exacerbated increase of ADMA in hypoxia (0.10±0.03 vs. 0.04±0.04 μmol/l; p&lt;0.02). Study participants carrying the minor allele of ARG1 rs2781667 had a relative risk of elevated mPAP (&gt;25 mm Hg) of 1.70 (1.56-1.85; p&lt;0.0001), and carriers of the minor allele of NOS3 rs2070744 had a relative risk of elevated mPAP (&gt;30 mm Hg) of 1.58 (1.47-1.69; p&lt;0.0001). The NOS3 and DDAH2 genes were associated with the incidence of acute mountain sickness. Conclusions: We conclude that genetic variability in the L-arginine / ADMA / NO pathway is an important determinant of high altitude pulmonary hypertension and acute mountain sickness. DDAH1 is linked to baseline ADMA, whilst DDAH2 determines the response of ADMA to hypoxia.

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.

The incidence, the most common symptoms and risk factors of altitude sickness in children

High-altitude tourism is gaining popularity. Mountains are also becoming an increasingly popular destination for school or family trips. This suggests that the number of children with high-altitude diseases, including acute mountain sickness (AMS), will also rise. The aim of this literature review was to determine the epidemiology of acute mountain sickness, its most common manifestations and risk factors in children. We analysed papers from the last 5 years, which were found by two independent authors using PubMed, ResearchGate and Google Scholar. The following keywords were used to identify relevant studies: acute mountain sickness, altitude sickness, children (by Medical Subject Headings). After screening with the exclusion criteria, the final analysis included 5 papers, which were assessed for the quality of evidence. The incidence of acute mountain sickness in children is 30–45% at elevations below 4,000 m. There were no differences compared to an adult population. Headache, sleep disorders and dizziness are the most common symptoms of acute mountain sickness in children. Further research is needed to identify factors that predispose children to this disease. In the light of the increasingly intensive alpine tourism among children, research on the sequelae of acute mountain sickness is recommended.

Effect Of Heat Acclimation On Incidence Of Acute Mountain Sickness During Exposure To Hypobaric Hypoxia (3,500 M)

INTRODUCTION: Adaptations gained from heat acclimation (HA) can induce protective responses to a different stressor, such as hypoxia. Rapid ascent to altitude (hypobaric hypoxia, HH) increases the risk for acute mountain sickness (AMS). However, it is unknown whether HA can protect against the development of AMS during exposure to HH. PURPOSE: To determine if prior HA reduces the incidence of AMS during a 30 hour exposure to HH (3,500 m). METHODS: Thirteen unacclimatized healthy men (mean ± SD; age: 21 ± 3 yr; ht: 172 ± 8 cm; wt: 75.1 ± 12.2 kg; sea level VO2peak 42.9 ± 4.6 ml·kg-1·min-1) participated in three study phases consisting of: Phase 1) baseline (pre HA) 30 hour HH exposure (HH1; 3,500 m), Phase 2) 14-day washout period during which volunteers completed an 8-day exercise-HA protocol (treadmill walking: 120 minutes at 5 km·hr-1, 2% grade; 40°C and 40% RH), and Phase 3) post HA 30 hour HH exposure (HH2). During the HA protocol, heart rate (HR) and core temperature (Tc) were recorded throughout exercise. AMS was assessed using the Environmental Symptoms Questionnaire after ~12, ~21, and ~23 hours of exposure during each HH phase. HR and pulse oxygen saturation (SpO2) were measured at rest immediately after assessment of AMS. A t-test was used to assess difference in HR and Tc from Day 1 and Day 8 of HA. For the HH exposures, HR and SpO2 data were analyzed by fitting a mixed effects model as implemented by GraphPad Prism 8.1.2. RESULTS: Heat acclimation was achieved as indicated by a lower Tc (Day 1: 38.1 ± 0.3 vs Day 8: 37.8 ± 0.3 °C; p<0.01) and HR (Day 1: 134 ± 17 vs Day 8: 121 ± 13 bpm; p<0.01) at the end of exercise on Day 8 compared to Day 1. Three of 13 volunteers developed AMS during HH1 but not during HH2. A fourth volunteer only developed AMS during HH2. From HH1 to HH2, resting HR (84 ± 6 vs 83 ± 7 bpm) and SpO2 (87 ± 2 vs 88 ± 2%) were not different (both p >0.05). CONCLUSION: Our results suggest that in unacclimatized individuals, HA may be an effective, though not perfect training strategy for reducing the incidence of AMS during rapid exposure to 3,500 m. Changes in AMS incidence could not be explained by alterations in HR or SpO2. Supported by USAMRDC; author views not official US Army or DoD policy.

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.

A Randomized Controlled Trial of the Lowest Effective Dose of Acetazolamide for Acute Mountain Sickness Prevention

BackgroundAcetazolamide is the most common medication used for acute mountain sickness prevention, with speculation that a reduced dose may be as efficacious as standard dosing with fewer side effects. MethodsThis double-blind, randomized, controlled noninferiority trial compared acetazolamide 62.5 mg twice daily to the standard dose acetazolamide 125 mg twice daily starting the evening prior to ascent from 1240 m (4100 ft) to 3810 m (12,570 ft) over 4 hours. The primary outcome was acute mountain sickness incidence (ie, headache, Lake Louise Questionnaire ≥3, and another symptom). ResultsA total of 106 participants were analyzed, with 51 (48%) randomized to 125 mg and 55 (52%) to 62.5 mg, with a combined acute mountain sickness incidence of 53 (50%) and mean severity of 3 (± 2.1). The 62.5-mg group failed to fall within the prespecified 26% noninferiority margin for acute mountain sickness incidence (62.5 mg = 30 [55%] vs 125 mg = 23 [45%], 95% confidence interval [CI] -11% to 30%). Participants in the 62.5-mg group had a higher risk of acute mountain sickness (odds ratio = 1.5, 95% CI 0.7-3.2) and moderate acute mountain sickness (odds ratio = 1.8, 95% CI 0.6-5.9), with a number needed to harm (NNH) of 9, with a number needed to treat (NNT) in the 125-mg group of 4.8. Increased acute mountain sickness incidence and symptom severity corresponded to lower weight-based and body mass index dosing, with similar side effects between groups. ConclusionAcetazolamide 62.5 mg twice daily failed to demonstrate equal effectiveness to 125 mg twice daily for prevention of acute mountain sickness. With increased risk and no demonstrable symptomatic or physiologic benefits, acetazolamide 62.5 mg twice daily should not be recommended for acute mountain sickness prevention.

Effect of 8 days of exercise-heat acclimation on aerobic exercise performance of men in hypobaric hypoxia.

Exercise-heat acclimation (EHA) induces adaptations that improve tolerance to heat exposure. Whether adaptations from EHA can also alter responses to hypobaric hypoxia (HH) conditions remains unclear. This study assessed whether EHA can alter time-trial performance and/or incidence of acute mountain sickness (AMS) during HH exposure. Thirteen sea-level (SL) resident men [SL peak oxygen consumption (V̇o2peak) 3.19 ± 0.43 L/min] completed steady-state exercise, followed by a 15-min cycle time trial and assessment of AMS before (HH1; 3,500 m) and after (HH2) an 8-day EHA protocol [120 min; 5 km/h; 2% incline; 40°C and 40% relative humidity (RH)]. EHA induced lower heart rate (HR) and core temperature and plasma volume expansion. Time-trial performance was not different between HH1 and HH2 after 2 h (106.3 ± 23.8 vs. 101.4 ± 23.0 kJ, P = 0.71) or 24 h (107.3 ± 23.4 vs. 106.3 ± 20.8 kJ, P > 0.9). From HH1 to HH2, HR and oxygen saturation, at the end of steady-state exercise and time-trial tests at 2 h and 24 h, were not different (P > 0.05). Three of 13 volunteers developed AMS during HH1 but not during HH2, whereas a fourth volunteer only developed AMS during HH2. Heat shock protein 70 was not different from HH1 to HH2 at SL [1.9 ± 0.7 vs. 1.8 ± 0.6 normalized integrated intensities (NII), P = 0.97] or after 23 h (1.8 ± 0.4 vs. 1.7 ± 0.5 NII, P = 0.78) at HH. Our results indicate that this EHA protocol had little to no effect-neither beneficial nor detrimental-on exercise performance in HH. EHA may reduce AMS in those who initially developed AMS; however, studies at higher elevations, having higher incidence rates, are needed to confirm our findings.

Hypoxic-inflammatory responses under acute hypoxia: In Vitro experiments and prospective observational expedition trial.

Induction of hypoxia-inducible-factor-1α (HIF-1α) pathway and HIF-target genes allow adaptation to hypoxia and are associated with reduced incidence of acute mountain sickness (AMS). Little is known about HIF-pathways in conjunction with inflammation or exercise stimuli under acute hypobaric hypoxia in non-acclimatized individuals. We therefore tested the hypotheses that (1) both hypoxic and inflammatory stimuli induce hypoxic-inflammatory signaling pathways in vitro, (2) similar results are seen in vivo under hypobaric hypoxia, and (3) induction of HIF-dependent genes is associated with AMS in 11 volunteers. In vitro, peripheral blood mononuclear cells (PBMCs) were incubated under hypoxic (10%/5% O2) or inflammatory (CD3/CD28) conditions. In vivo, Interleukin 1β (IL-1β), C-X-C Chemokine receptor type 4 (CXCR-4), and C-C Chemokine receptor type 2 (CCR-2) mRNA expression, cytokines and receptors were analyzed under normoxia (520 m above sea level (a.s.l.)), hypobaric hypoxia (3883 m a.s.l.) before/after exercise, and after 24 h under hypobaric hypoxia. In vitro, isolated hypoxic (p = 0.004) or inflammatory (p = 0.006) stimuli induced IL-1β mRNA expression. CCR-2 mRNA expression increased under hypoxia (p = 0.005); CXCR-4 mRNA expression remained unchanged. In vivo, cytokines, receptors, and IL-1β, CCR-2 and CXCR-4 mRNA expression increased under hypobaric hypoxia after 24 h (all p ≤ 0.05). Of note, proinflammatory IL-1β and CXCR-4 mRNA expression changes were associated with symptoms of AMS. Thus, hypoxic-inflammatory pathways are differentially regulated, as combined hypoxic and exercise stimulus was stronger in vivo than isolated hypoxic or inflammatory stimulation in vitro.

P6480Asymmetric dimethylarginine (ADMA) predicts altitude-associated hypoxic pulmonary arterial hypertension

Abstract Prolonged exposure to altitude-associated chronic hypoxia (CH) may cause high altitude pulmonary hypertension (HAPH). Chronic intermittent hypobaric hypoxia (CIH) occurs in individuals who commute between sea level and high altitude. CIH is associated with repetitive acute hypoxic acclimatization and conveys the long-term risk of HAPH. As nitric oxide (NO) is an important regulator of systemic and pulmonary vascular tone and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis that increases in hypoxia, we aimed to investigate whether ADMA predicts the incidence of HAPH among Chilean frontiers personnel exposed to six months of CIH. We performed a prospective study of 123 healthy male subjects who were subjected to CIH (5 days at appr. 3,550 m, followed by 2 days at sea level) for six months. ADMA, SDMA, L-arginine, arterial oxygen saturation, systemic arterial blood pressure, and haematocrit were measured at baseline and at months 1, 4, and 6 at high altitude. Acclimatization to high altitude was determined using the Lake Louise Score and the presence of acute mountain sickness (AMS). Echocardiography was performed after six months of CIH in a subgroup of 43 individuals with either good (n=23) or poor (n=20) aclimatization to altitude, respectively. Logistic regression was used to assess the association of biomarkers with HAPH. 100 study participants aged 18.3±1.3 years with complete data sets were included in the final analysis. Arterial oxygen saturation decreased upon the first ascent to altitude and plateaued at about 90% during the further course of the study. Haematocrit increased to about 47% after one month and remained stable thereafter. ADMA continuously increased and SDMA decreased during the study course, whilst L-arginine levels showed no distinct pattern. The incidence of AMS and the Lake Louise Score were high after the first ascent (53 and 3.1±2.4, respectively) and at one month of CIH (47 and 3.0±2.6, respectively), but decreased to 20 and 1.4±2.0 at month 6, respectively (both p&lt;0.001 for trend). In echocardiography, 18 participants (42%) showed a mean pulmonary arterial pressure (mPAP) greater than 25 mm Hg (mean ± SD, 30.4±3.9 mm Hg), out of which 9 (21%) were classified as HAPH (mPAP ≥30 mm Hg; mean ± SD, 33.9±2.2 mm Hg). Baseline ADMA, but not SDMA, was significantly associated with mPAP at month 6 in univariate logistic regression analysis (R = 0.413; p=0.007). In ROC analysis, a cut-off for baseline ADMA of 0.665 μmol/l was determined as the optimal cut-off level to predict HAPH (mPAP &gt;30 mm Hg) with a sensitivity of 100% and a specificity of 63.6%. ADMA concentration increases during long-term CIH. It is an independent predictive biomarker for the incidence of HAPH. SDMA concentration decreases during CIH and shows no association with HAPH. Our data support a role of impaired NO-mediated pulmonary vasodilation in the pathogenesis of high altitude pulmonary hypertension. Acknowledgement/Funding CONICYT/FONDEF/FONIS Sa 09I20007; FIC Tarapaca BIP 30477541-0; BMBF grant 01DN17046 (DECIPHER); Georg &amp; Jürgen Rickertsen Foundation, Hamburg

Relationship of Activity Patterns to Acute Mountain Sickness in South Pole Workers.

This study aimed to evaluate the influence of physical activity on incidence of acute mountain sickness (AMS) by continuous activity monitoring in a free-living sample of South Pole workers over the initial 72 h at altitude exposure of 2,840 m (9,318 ft). Body Media activity monitors were worn by 47 healthy participants. AMS was defined by the Lake Louise symptom questionnaire. Venous blood samples were taken at sea level and approximately 48 h after high altitude exposure. AMS incidence was 34% (n=16/47) over the first 48 h and 40% (n=19/47) over 72 h. On day 2 at high altitude, individuals with AMS demonstrated a significantly greater increase in the percent change in physical activity metrics from baseline: total energy expenditure 19±13 vs. 5±7%, total steps 65±51 vs. 10±18%, metabolic equivalent of tasks 21±13 vs. 7±13%, and time spent performing moderate to vigorous physical activity 114±79 vs. 26±27% for individuals with AMS vs. no AMS, respectively, p<0.05. In addition, erythropoietin and vascular endothelial growth factor were 1.69 and 1.75 times higher, respectively, in those with AMS. In conclusion, workers who engaged in increased physical activity and activity intensity during initial exposure to the South Pole were more susceptible to developing AMS.

Altitude Sickness Prevention with Ibuprofen Relative to Acetazolamide

BackgroundAcute mountain sickness is a common occurrence for travel to high altitudes. Although previous studies of ibuprofen have shown efficacy for the prevention of acute mountain sickness, recommendations have been limited, as ibuprofen has not been compared directly with acetazolamide until this study. MethodsBefore their ascent to 3810 m on White Mountain in California, adult volunteers were randomized to ibuprofen (600 mg, 3 times daily, started 4 hours before the ascent), or to acetazolamide (125 mg, twice daily, started the night before the ascent). The main outcome measure was acute mountain sickness incidence, using the Lake Louise Questionnaire (LLQ), with a score of >3 with headache. Sleep quality and headache severity were measured with the Groningen Sleep Quality Survey (GSQS). This trial was registered at ClinicalTrials.gov: NCT03154645 ResultsNinety-two participants completed the study: 45 (49%) on ibuprofen and 47 (51%) on acetazolamide. The total incidence of acute mountain sickness was 56.5%, with the incidence for the ibuprofen group being 11% greater than that for acetazolamide, surpassing the predetermined 26% noninferiority margin (62.2% vs 51.1%; 95% confidence interval [CI], –11.1 to 33.5). No difference was found in the total LLQ scores or subgroup symptoms between drugs (P = .8). The GSQS correlated with LLQ sleep (r = 0.77; 95% CI, 0.67–0.84)=%. The acetazolamide group had higher peripheral capillary oxygen saturation than the ibuprofen group (88.5% vs 85.6%; P = .001). ConclusionIbuprofen was slightly inferior to acetazolamide for acute mountain sickness prevention and should not be recommended over acetazolamide for rapid ascent. Average symptoms and severity were similar between drugs, suggesting prevention of disease.

High-altitude illness in the pediatric population: a review of the literature on prevention and treatment.

Increasing numbers of children are now traveling to high-altitude destinations, and pediatricians often see these children prior to and immediately following their travels. Thus, pediatricians have the opportunity to provide guidance for the prevention of altitude illness and must treat high-altitude illness (HAI) in some circumstances. This review will examine guidelines for prevention and management of HAI in the pediatric population. Recent research has examined children's short-term cardiorespiratory adaptation to high altitude, incidence of acute mountain sickness, hypoxic ventilator response, and maximal exercise capacity. Overall, studies indicate that children and adults are largely similar in these variables. Furthermore, studies suggest that heritability seems to be a component of response to altitude and development of altitude illness - a finding that may have implications for family vacation planning. Increasing numbers of children are visiting high altitude destinations. Whereas most of these child travelers will only experience mild to moderate symptoms of HAI, a small percentage, particularly those with predisposing health conditions, may experience severe disease. Pediatricians should encourage preventive measures with an emphasis on gradual ascent and vigilance for onset of symptoms that should prompt immediate transport to medical care.