Severe acute mountain sickness and suspect high altitude cerebral edema related to nitroglycerin use

An elite mountaineer reported severe acute mountain sickness and ataxia during an 8000-m expedition and concomitant use of transdermal nitroglycerin patches aimed to prevent frostbites. Use of nitroglycerin for this purpose is off-label, and its safety has not been assessed. Moreover, a relation between nitrate-induced cerebral vasodilation and high altitude cerebral edema is theoretically possible on a pathophysiological basis. It is our opinion that nitroglycerin use at high altitude should be discouraged, as efficacy in the prevention of frostbites is questionable and safety has not been assessed.     

Endocrine aspects of high altitude acclimatization and acute mountain sickness

The acute acclimatization to high altitude is underpinned by a diuresis (and to a lesser extent a natriuresis) that facilitates a reduction in plasma volume. This allows a haemoconcentration to occur that increases the oxygen carrying capacity of a given volume of blood, a vital effect in the presence of a reduced partial pressure of oxygen. This critical acclimatization process is orchestrated by the endocrine system. This review will present the key evidence regarding the changes in several important hormones that affect this process.     

黄芩苷与红景天胶囊对急性高原病预防作用比较

 目的 探讨黄芩苷胶囊对急性高原病(acute mountain sickness, AMS)的预防作用。方法 采用随机对照的研究方法, 80名急进高原健康男性青年随机分为3组, 黄芩苷组(n=32)、红景天组(n=24)和安慰剂组(n=24)。3组在进入高原前2 d、进入高原后连续3 d分别服用黄芩苷胶囊(0.5 g, 2次/d)、红景天胶囊(0.76 g, 2次/d)和安慰剂(2粒, 2次/d)。检测急进高原前(海拔397 m)和急进高原后(3658 m)受试者氧饱和度、心率、收缩压、舒张压, 彩色多普勒超声测量肺动脉收缩压(pulmonary artery systolic pressure, PASP)和平均肺动脉压(mean pulmonary arterial pressure, MPAP), 统计急进高原后各组的AMS发病率。结果 急进高原后安慰剂组、黄芩苷组和红景天组的AMS发病率分别为58.3%(14/24)、25.0%(8/32)和29.2%(7/24), 与安慰剂组比较, 黄芩苷组及红景天组AMS发病率明显降低, 差异有统计学意义(P<0.05)。与急进高原前比较, 各组受试者急进高原后心率、血压及肺动脉压均升高, 氧饱和度降低(P<0.05);与安慰剂组比较, 黄芩苷组血压及心率明显降低(P<0.05), 红景天组急进高原后氧饱和度升高、肺动脉压降低(P<0.05)。结论 黄芩苷组可能通过降低血压及心率预防AMS的发生, 红景天胶囊可能通过升高氧饱和度, 降低PASP、MPAP预防AMS的发生。     

Cognitive changes at high altitude in healthy climbers and in climbers developing acute mountain sickness

We report the cognitive functions of 17 non-acclimatized mountaineers who ascended from low lands to an altitude of 4,559 m in 24 h and were studied there within 6 h. We found that this rapid ascent to high altitude had small, but differential effects upon cognitive performance depending upon the later development of acute mountain sickness (AMS). Subjects who developed AMS within a 24-48-h stay at high altitude were mildly impaired in short term memory, but improved in conceptual tasks, while subjects who remained healthy had a better short term memory performance but no improvement in cognitive flexibility. Possible explanations for these unexpected effects of high altitude are discussed.     

Symptoms of acute mountain sickness in Sherpas exposed to extremely high altitude

Droma, Yunden, Masayuki Hanaoka, Buddha Basnyat, Amit Arjyal, Pritam Neupane, Anil Pandit, Dependra Sharma, and Keishi Kubo. Symptoms of acute mountain sickness in Sherpas exposed to extremely high altitude. High Alt. Med. Biol. 7:312-314, 2006.--The aim of this field interview was to investigate the current state of affairs concerning acute mountain sickness (AMS) in high-altitude residents, specifically the Sherpas at 3440 m above sea level, when they are exposed rapidly to altitudes significantly higher than their residing altitudes. Out of 105 Sherpas (44 men and 61 women, 31.2 +/- 0.8 yr), 104 had mountain-climbing experiences to 5701.4 +/- 119.1-m altitude in average 3.5 times each year. On the other hand, only 68 out of 111 non-Sherpas (29.9 +/- 0.8 yr) had experience of 1.4 +/- 1.5 climbs to an average 2688.6 +/- 150.4-m altitude in their mountaineering histories (p < 0.0001). Among the 104 Sherpas, 45 (43.3%) complained of at least one AMS symptom (headache, gastrointestinal symptoms, weakness, dizziness, and difficulty sleeping) in their experiences of mountaineering at an average 5518.9 +/- 195.9-m altitude. And 16 out of the 68 non-Sherpas (23.5%) reported the AMS symptoms at a mean altitude of 2750.0 +/- 288.8 m. Moreover, we also noticed that the Sherpa women showed a significantly higher Sa(O(2) ) (93.9 +/- 0.2%) than did Sherpa men (92.4 +/- 0.3%, p = 0.0001) at an altitude of 3440 m. The brief field interview evidenced that Sherpas might suffer from AMS when exposed to altitudes significantly higher than their residing altitude.     

A Tibetan with chronic mountain sickness followed by high altitude pulmonary edema on reentry

Chronic mountain sickness (CMS) and high altitude pulmonary edema (HAPE) each occur rarely in Tibetans, and they have previously not been reported in the same person. Here we describe a 37-year-old native Tibetan man with CMS at 4300 m, who developed HAPE after his return home from a 12-day visit to sea level. Possible common pathogenetic factors included a poor ventilatory response to hypoxia, accentuated hypoxemia, pulmonary hypertension, and increased blood volume. In addition, strenuous exercise and high levels (to approximately 1000 ng/L) of plasma atrial natriuretic peptide may have contributed to HAPE.     

Elevated plasma cholecystokinin at high altitude: metabolic implications for the anorexia of acute mountain sickness

The aims of the present study were to measure the satiety neuropeptide cholecystokinin (CCK) in humans at terrestrial high altitude to investigate its possible role in the pathophysiology of anorexia, cachexia, and acute mountain sickness (AMS). Nineteen male mountaineers aged 38 +/- 12 years participated in a 20 +/- 5 day trek to Mt. Kanchenjunga basecamp (BC) located at 5,100 m, where they remained for 7 +/- 5 days. Subjects were examined at rest and during a maximal exercise test at sea-level before/after the expedition (SL1/SL2) and during the BC sojourn. There was a mild increase in Lake Louise AMS score from 1.1 +/- 1.2 points at SL1 to 2.3 +/- 2.3 points by the end of the first day at BC (P < 0.05). A marked increase in resting plasma CCK was observed on the morning of the second day at BC relative to sea-level control values (62.9 +/- 42.2 pmol/L(-1) vs. SL1: 4.3 +/- 8.3 pmol/L(-1), P < 0.05 vs. SL2: 26.5 +/- 25.2 pmol/L(-1), P < 0.05). Maximal exercise increased CCK by 78.5 +/- 24.8 pmol/L(-1), (P < 0.05 vs. resting value) during the SL1 test and increased the plasma concentration of non-esterified fatty acids and glycerol at BC (P < 0.05 vs. SL1/SL2). The CCK response was not different in five subjects who presented with anorexia on Day 2 compared with those with a normal appetite. While there was no relationship between the increase in CCK and AMS score at BC, a more pronounced increase in resting CCK was observed in subjects with AMS (> or =3 points at the end of Day 1 at BC) compared with those without (+98.9 +/- 1.4 pmol/L(-1) vs. +67.6 +/- 37.2 pmol/L(-1), P < 0.05). Caloric intake remained remarkably low during the stay at BC (8.9 +/- 1.4 MJ.d(-1)) despite a progressive decrease in total body mass (-4.5 +/- 2.1 kg after 31 +/- 13 h at BC, P < 0.05 vs. SL1/SL2), which appeared to be due to a selective loss of torso adipose tissue. These findings suggest that the satiogenic effects of CCK may have contributed to the observed caloric deficit and subsequent cachexia at high altitude despite adequate availability of palatable foods. The metabolic implications of elevated CCK in AMS remain to be elucidated.     

Ocular functions and incidence of acute mountain sickness in women at altitude

The effects of altitude on a series of ocular functions were studied on seven expedition members, all women aged 23-53 years, during the first ascent of the 6798-m peak Brigupanth in the Indian Himalayas. The only consistent change was a decrease in convergence amplitude. The amplitude of accommodation remained stable among the younger climbers, but decreased markedly among the older ones as higher altitudes were reached. There also appeared to be a lessened vascular reactivity to the hypoxia of altitude in the older members. Stereoscopic vision was unimpaired at all altitudes tested and extra-ocular muscle balance remained unaffected in all but two members who had an increase in their baseline phorias. Two of the summit climbers developed retinal hemorrhages. There was an average weight loss of 5.4 kg during the climb, but general health was good. Symptoms of acute mountain sickness were noted infrequently, and there were only moderate changes in the menstrual cycle.     

Acute mountain sickness in a subject with metabolic syndrome at high altitude

Abstract Strapazzon, Giacomo, Annalisa Cogo, and Andrea Semplicini. Acute mountain sickness in a subject with metabolic syndrome at high altitude. High Alt. Med. Biol. 9:245-248, 2008.-Visitors at high altitude are increasing in age and comorbidities, which can lead to a failure in acclimatization. We describe the development of acute mountain sickness (AMS) in a 44-year-old man with metabolic syndrome and the time- and altitude-dependent correlation between the development of AMS and blood pressure and heart rate changes. Our observations support a dominant role of endothelial dysfunction in the pathogenesis of AMS and suggest new behavioral indications.     

Acute mountain sickness; prophylactic benefits of antioxidant vitamin supplementation at high altitude

Acute mountain sickness; prophylactic benefits of Free-radical-mediated damage to the blood-brain barrier may be implicated in the pathophysiology of acute mountain sickness (AMS). To indirectly examine this, we conducted a randomized double-blind placebo-controlled trial to assess the potentially prophylactic benefits of enteral antioxidant vitamin supplementation during ascent to high altitude. Eighteen subjects aged 35 +/- 10 years old were randomly assigned double-blind to either an antioxidant (n = 9) or placebo group (n = 9). The antioxidant group ingested 4 capsules/day(-1) (2 after breakfast/2 after evening meal) that each contained 250 mg of L-ascorbic acid, 100 IU of dl-a-tocopherol acetate and 150 mg of alpha-lipoic acid. The placebo group ingested 4 capsules of identical external appearance, taste, and smell. Supplementation was enforced for 3 weeks at sea level and during a 10-day ascent to Mt. Everest base camp (approximately 5,180 m). Antioxidant supplementation resulted in a comparatively lower Lake Louise AMS score at high altitude relative to the placebo group (2.8 +/- 0.8 points versus 4.0 +/- 0.4 points, P = 0.036), higher resting arterial oxygen saturation (89 +/- 5% versus 85 +/- 5%, P = 0.042), and total caloric intake (13.2 +/- 0.6 MJ/day(-1) versus 10.1 +/- 0.7 MJ/day(-1), P = 0.001); the latter is attributable to a lower satiety rating following a standardized meal. These findings indicate that the exogenous provision of water and lipid-soluble antioxidant vitamins at the prescribed doses is an apparently safe and potentially effective intervention that can attenuate AMS and improve the physiological profile of mountaineers at high altitude.     

Diurnal variations of acute mountain sickness, colour vision, and plasma cortisol and ACTH at high altitude

Time dependence of colour vision in the green/red axis, signs of acute mountain sickness (AMS), and plasma cortisol and ACTH concentrations were studied in eight sea-level male natives exposed 79 h to altitude hypoxia at 4,350 m. Colour vision (CV) was explored every 2 h from 08:00 to 20:00 hours by means of two portable anomaloscopes, one derived from Essilor CHROMOTEST and the other from the OSCAR. Significant diurnal variations in CV were found using both anomaloscopes, major alterations in green relative to red sensitivity being seen in the early morning. AMS scores also showed remarkable diurnal variations, parallel to those of plasma cortisol and CV, with maximum values observed at 08:00 hours. Cortisol diurnal rhythm was maintained in hypoxia, with mean concentrations higher than in normoxia. ACTH followed the same trend, but variations were not significant. Significant correlations were found between instant values of CV, cortisol, and AMS score, but no causal relationship between these variables can be ascertained.     

高原脑水肿的CT研究

在青藏高原,随着西部大开发和高原旅游业的发展,高原脑水肿(high altitude cerebral edema,HACE)时有发生,患病率为0.5%～2.O%[1].HACE是急性高山病(acute mountain sickness,AMS)最为凶险的终末阶段,发病机制可能与缺氧导致脑充血水肿、颅内压升高和细胞功能障碍有关,确切机制尚不十分明了[2].     

高原脑水肿的MRI诊断

目的:分析高原脑水肿(high altitude cerebra edema,HACE)的MRI表现,以提高对本病诊断的准确性。方法:对13例高原脑水肿患者行头颅MRI横断位SE序列(T1WI、T2WI)、水抑制(FLAIR)及矢状位SE序列(T1WI)扫描,对其MRI表现进行回顾性分析。结果:高原脑水肿MRI表现:T1WI为低信号,T2WI为高信号,信号较均匀,边缘不清,FLAIR为较均匀高信号。13例双侧大脑半球白质对称性水肿,5例大脑灰质水肿,12例胼胝体水肿,3例丘脑水肿,3例脑干水肿,9例小脑水肿,11例侧脑室变窄,12例脑沟变窄,5例脑裂变窄。结论:高原脑水肿于MRI呈弥漫性改变,大脑、胼胝体、丘脑、脑干、小脑均可受累,以胼胝体为中心,为多种类型并存的脑水肿,有一定的特征性。MRI能正确诊断高原脑水肿提供依据。     

急性高原反应症状及体征变化对高原脑水肿早期诊断意义的研究

目的观察和随访急进高原后疑似高原脑水肿者（HACE）的症状、体征变化,为制定HACE的早期诊断标准提供依据。方法对24200名急进高原人员进行筛查,对其中162例HACE疑似病例进行观察随访,总结急进高原1w内的症状、体征变化。结果在这些HACE疑似病例中,有36例最后确诊为HACE。HACE患者早期头痛、呕吐（症状评分≥4）以及呼吸困难、胸闷、咳嗽、紫绀发生率明显高于非HACE组（P〈0．05）,且经休息及对症治疗后无缓解;HACE发病高峰为急性高原暴露24—72h。结论严重头痛、呕吐症状的出现与早期HACE发病密切相关,尤其当这些症状经15—24h单纯卧床、小流量吸氧及对症治疗后无明显缓解时,应警惕早期HACE的发生。     

Effects of propranolol on acute mountain sickness (AMS) and well-being at 4,300 meters of altitude

A number of physiological responses and adjustments occur at high altitude to compensate for hypoxia. We hypothesized that interference with one component of the normal compensatory process, the sympathetic nervous system, would hinder altitude acclimatization and thereby exacerbate acute mountain sickness (AMS) and compromise well-being. Twelve young males (21.2 +/- 0.4 years) received either 80 mg propranolol (PRO; n = 6) or placebo (PLA; n = 6), t.i.d. at sea level (SL) and during the first 15 d of a 19-d residence at 4,300 m (HA). Individuals were randomly assigned to each group. The Environmental Symptoms Questionnaire (ESQ) was administered at SL and twice daily (AM and PM) during the entire altitude exposure in order to assess AMS symptoms and subjective feelings of well-being. Supine heart rate (HR) was determined at rest twice at SL and four times at HA. HR in the PLA group increased 40% over SL values (57 +/- 3 to 80 +/- 4 beats/min) by day 7 at HA (p less than 0.01). HR in the PRO group did not increase above SL values during medication at HA. By 4 d after the medication administration was terminated, HR in the PRO group had increased and did not differ from the PLA group. Throughout the entire altitude exposure, ESQ scores for the PRO group were lower than or similar to the PLA group. Furthermore, cessation of PRO treatment did not result in a change in well-being. These findings suggested that interference with the normal acclimatization process by beta-adrenergic blockade did not exacerbate AMS or reduce feelings of well-being.     

高原脑水肿的MRI检查方法

目的：探讨MRI(核磁共振成像)在高原脑水肿检查中的运用，总结适合高原脑水肿检查的序列。方法：对9例高原脑水肿患者12次MRI检查进行回顾，对比T1WI、T2WI、水抑制FIR、扩散加权LSDW等序列在横断、矢状及冠状扫描所成图像分析。结果：T1WI、T2WI序列可充分显示高原脑水肿形成的大脑形态、结构和信号改变IFIR序列能够抑制掉T2WI图像中脑脊液形成的高信号，更好的显示病变脑组织；LSDW序列能够从分子水平显示早期脑缺血缺氧改变，矢状面、冠状面检查能够显示脑水肿造成的大脑形态、结构的异常改变和发现脑疝的存在。结论：横断位T1WI、T2WI、FIR序列检查可以作为高原脑水肿的常规检查序列，横断面LSDW序列可以作为补充检查方法。必要时可以进行矢状面及冠状面检查。     

Association between physiological responses after exercise at low altitude and acute mountain sickness upon ascent is sex-dependent

Background:Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses,and consists of nonspecific symptoms when unacclimatized persons ascend to elevation of ≥2500 m.Risk factors of AMS include:the altitude,individual susceptibility,ascending rate and degree of pre-acclimatization.In the current study,we examined whether physiological response at low altitude could predict the development of AMS.Methods:A total of 111 healthy adult healthy volunteers participated in this trial;and 99 (67 men and 32 women)completed the entire study protocol.Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude (500m).Heart rate,blood pressure (BP) and pulse oxygen saturation (SpO2)were recorded prior to and during the last minute of exercise.The ascent from 500m to 4100m was completed in 2 days.AMS was defined as ≥3 points in a 4-item Lake Louise Score,with at least one point from headache wat 6-8 h after the ascent.Results:Among the 99 assessable subjects,47 (23 men and 24 women) developed AMS at 4100 m.In comparison to the subjects without AMS,those who developed AMS had lower proportion of men (48.9％ vs.84.6％,P＜0.001),height(168.4±5.9cm vs.171.3±6.1cm,P=0.019),weight (62.0±10.0kg vs.66.7±8.6kg,P=0.014) and proportion of smokers(23.4％ vs.51.9％,P=0.004).Multivariate regression analysis revealed the following independent risks for AMS:female sex (odds ratio (OR)=6.32,P＜0.001),SpO2 change upon exercise at low altitude (OR=0.63,P=0.002) and systolic BP change after the ascent (OR=0.96,P=0.029).Women had larger reduction in SpO2 after the ascent,higher AMS percentage and absolute AMS score.Larger reduction of SpO2 after exercise was associated with both AMS incidence(P=0.001) and AMS score (P＜0.001) in men but not in women.Conclusions:Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent.Such an association was more robust in men than in women.Trial registration:Chinese Clinical Trial Registration,ChiCTR1900025728.Registered 6 September 2019.     

特高海拔14例急性高原肺水肿救治体会

目的 总结在特高高原组织救治急性肺水肿的经验教训.方法 对2009年7月在海拔5400 m高原所发生的14例急性高原肺水肿(4例合并急性高原脑水肿)救治经过进行回顾总结.结果 1例急性肺水肿患者在由基层部队组织后送途中死亡,其余13例由驻军医院组织低转至医疗站(海拔3700 m)均治愈.结论 在特高海拔地区,早期诊断、就地治疗、前接后送、阶梯治疗是提高救治水平的关键措施.     

Ataxia: an early indicator in high altitude cerebral edema

Wu, Tianyi, Shouquan Ding, Jinliang Liu, Jianhou Jia, Ruichen Dai, Baozhu Liang, Jizhui Zhao, and Detang Qi. Ataxia: an early indicator in high altitude cerebral edema. High Alt. Med. Biol. 7:275-280, 2006.--As a result of industrial development in the western region of China, in 2001 the Chinese government decided to build Qinghai-Tibetan Railway. The new railroad stretches 1118 km from Golmud (2808 m) to Lhasa (3658 m), with more than three-quarter of the distance above 4000 m, through the Mt. Kun Lun and Tanggula ranges. From the beginning of the project on June, 29, 2001, to the end of the year of 2003, about 74,735 construction workers worked in the harsh climate, in adverse circumstances and a low-barometric-pressure environment. The construction provided an opportunity for the investigation and study of acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE). These altitude illnesses were very common in the construction workers. From July 1, 2001, to October 31, 2003, the overall incidence of AMS, HAPE, and HACE in the total workers was approximately 45%-95%, 0.49%, and 0.26%, respectively. Altitude illnesses were studied at two hospitals near the construction site. One hospital is located on the Fenghuoshan (Mt. Wind-gap) at an altitude of 4779 m (PB 428 torr), and the second hospital is situated in the Kekexili area at an altitude of 4505 m (PB 440 torr). Kekexili is a sparsely populated zone because the weather conditions are very bad all year round. These two hospitals received patients from the construction sites, where workers were working at altitudes between 4464 and 4905 m. A total of 8014 workers were treated at Fenghuoshan and 5488 were in Kekexili over the past 3 years. According to local guidance about proper medical care, workers ascending to high altitude should be examined physically, complete an AMS questionnaire, and be monitored for ataxia as an early warning sign of the impending, more serious aspects of HACE. The onset of HACE is frequently characterized by an ataxic gait, as reported since the middle of the 20th century (Gray et al., 1971; Wilson, 1973; Houston and Dickinson, 1975; Dickinson, 1979; Clarke, 1988; Hackett and Oelz, 1992; Hackett, 2002; Hackett and Roach, 2004). However, there are no detailed analyses of ataxia in HACE. This paper considers the relation between ataxia and HACE and its frequency, significance, and importance.