Altitude illness: update on prevention and treatment

ABSTRACT: Altitude illness is a broad category of disease encompassing acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) that can affect persons who travel to altitude without adequate acclimatization. Initial symptoms of AMS and the more serious HACE or HAPE can be subtle, and it is important that the practitioner be able to recognize and differentiate between these diagnoses because they can progress rapidly and be fatal if untreated. There are well-established criteria and many proven therapies both for prophylaxis and treatment of altitude illness; however, despite intense research efforts, the specific mechanisms of these complex diseases remain elusive. Adequate acclimatization via controlled ascent remains the most important factor in preventing altitude illness, although prophylactic pharmacotherapy also may be useful. Rapid descent remains the most important treatment factor, although treatment at altitude with various therapies is possible for mild cases with adequate resources.     

对快速进入高原部队预防急性高原病的措施探讨

目的了解急性高原病(AMS)的发病情况并探讨其预防措施。方法2006—2007年两次进入高原某地进行军事演练,伴随卫勤保障任务,通过在平原集结时之前,进行身体调整,加大训练强度,进入高原后,延长休整天数,进行心理干预,开展AMS知识的宣传教育,采用问卷、卫生队、卫生室进行病员登统计、个别问诊、检查的方法,了解部队进入高原后AMS的发病情况。结果2006年9—10月份与2007年9—10月份两次进入高原人员年龄分布无统计学差异(P>0.05),而发病率由21.6%下降为13.4%及住院率0.72%下降为0.48%,2007年9—10月份与2006年9—10月份重度急性高原反应、高原肺水肿和高原脑水肿发病率都有所减低。结论在常规的卫勤保障基础上,应调整进入高原的休整期,一般7d左右为宜,加强高原卫生宣传教育,正确引导官兵们对低氧危害性和机体代偿能力的认识,克服高原恐惧心理和麻痹大意思想;提高医务人员的业务水平,增强责任心。这样可以大大地降低AMS的发病率和住院率,有效地保障官兵的身体健康。     

Evidence for a genetic basis for altitude-related illness

Altitude-related illnesses are a family of interrelated pulmonary, cerebral, hematological, and cardiovascular medical conditions associated with the diminished oxygen availability at moderate to high altitudes. The acute forms of these debilitating and potentially fatal conditions, which include acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE), often develop in incompletely acclimatized lowlanders shortly after ascent, whereas, the chronic conditions, such as chronic mountain sickness (CMS) and high altitude pulmonary hypertension (HAPH), usually afflict native or long-term highlanders and may reflect a loss of adaptation. Anecdotal reports of particularly susceptible people or families are frequently cited as evidence that certain individuals have an innate susceptibility (or resistance) to developing these conditions and, in recent decades, there have been a number of studies designed to characterize the physiology of individuals predisposed to these conditions, as well as to identify the specific genetic variants that contribute to this predisposition. This paper reviews the epidemiological evidence for a genetic component to the various forms of altitude-related illness, such as innate susceptibility, familial clustering, and patterns of population susceptibility, as well as the molecular evidence for specific genetic risk factors. While the evidence supports some role for genetic background in the etiology of altitude-related illness, limitations in individual studies and a general lack of corroborating research limit the conclusions that can be drawn about the extent of this contribution and the specific genes or pathways involved. The paper closes with suggestions for future work that could support and expand on previous studies, as well as provide new insights.     

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.     

Sildenafil citrate for the prevention of high altitude hypoxic pulmonary hypertension: double blind, randomized, placebo-controlled trial

Exaggerated hypoxic pulmonary vasoconstriction is a key factor in the development of high altitude pulmonary edema (HAPE). Due to its effectiveness as a pulmonary vasodilator, sildenafil has been proposed as a prophylactic agent against HAPE. By conducting a parallel-group double blind, randomized, placebo-controlled trial, we investigated the effect of chronic sildenafil administration on pulmonary artery systolic pressure (PASP) and symptoms of acute mountain sickness (AMS) during acclimatization to high altitude. Sixty-two healthy lowland volunteers (36 male; median age 21 years, range 18 to 31) on the Apex 2 research expedition were flown to La Paz, Bolivia (3650?m), and after 4-5 days acclimatization ascended over 90?min to 5200?m. The treatment group (n=20) received 50?mg sildenafil citrate three times daily. PASP was recorded by echocardiography at sea level and within 6?h, 3 days, and 1 week at 5200?m. AMS was assessed daily using the Lake Louise Consensus symptom score. On intention-to-treat analysis, there was no significant difference in PASP at 5200?m between sildenafil and placebo groups. Median AMS score on Day 2 at 5200?m was significantly higher in the sildenafil group (placebo 4.0, sildenafil 6.5; p=0.004) but there was no difference in prevalence of AMS between groups. Sildenafil administration did not affect PASP in healthy lowland subjects at 5200?m but AMS was significantly more severe on Day 2 at 5200?m with sildenafil. Our data do not support routine prophylactic use of sildenafil to reduce PASP at high altitude in healthy subjects with no history of HAPE. TRIALS REGISTRATION NUMBER: NCT00627965.     

Evidence for increased intracranial pressure in high altitude pulmonary edema

We sought to determine if optic nerve sheath diameter (ONSD), a surrogate measure of ICP, is increased in high altitude pulmonary edema (HAPE). Five HAPE patients (one with a codiagnosis of high altitude cerebral edema [HACE]) treated at the Himalayan Rescue Association clinic in Pheriche, Nepal (4240 m), underwent optic nerve sheath ultrasonography (ONSU) at admission to determine ONSD. Results were compared to ONSD in 32 control subjects at the same altitude without evidence of altitude illness. Four of the five HAPE patients underwent repeat ONSU at discharge. All exams were read by two blinded observers. The mean ONSD for HAPE patients on presentation was 5.7 +/- 0.44 mm and for controls was 4.7 +/- 0.56 mm (p = 0.003). Excluding the patient with a coexistent clinical diagnosis of HACE, mean ONSD at presentation for the other four HAPE patients was 5.7 +/- 0.50 mm and was significantly different from controls (p = 0.007). In the four HAPE patients with repeat exams, ONSD decreased by 17% +/- 15% (95% CI 4-30%) between admission and discharge. We conclude that HAPE is associated with increased ONSD, a surrogate measure of increased ICP.     

Effects of slow ascent to 4559 M on fluid homeostasis.

Since acute mountain sickness (AMS) is associated with rapid ascent and with fluid retention, we assessed clinical status and fluid homeostasis in men slowly ascending on foot over 3 d to 4559 m and remaining at this altitude 5 d. We studied 15 male mountaineers, 6 of whom had previously had repeated, severe AMS or high altitude pulmonary edema (HAPE), at 1170 m, 3611 m, and 4559 m. We found that four of the six subjects with previous AMS or HAPE compared with none of nine with no such history, developed these conditions. Those who remained well had a diuresis that could not be overcome by increasing fluid intake and no change in renin activity, plasma aldosterone, or atrial natriuretic peptide (ANP). Those who became ill showed considerable weight gain independent of fluid intake, and a great increase in ANP which correlated with measurements of right atrial cross section. We conclude that mountaineers who have previously experienced repeated AMS or HAPE get fluid retention despite slow ascent and that this is associated with widening of the atrium and an increase in ANP.     

Erythropoietin levels in lowlanders and high-altitude natives at 3450 m

BACKGROUND: This study is aimed to determine whether short or prolonged residency at high altitude (HA) elicits erythropoietin (EPO) secretion effectively in subjects who were able to acclimatize and those who were not able to acclimatize and suffered from acute mountain sickness (AMS) and high altitude pulmonary edema (HAPE). METHODS: Plasma EPO was measured in 16 lowland residents (LLR) at sea level (SL) and during 11 d of their sojourn at an altitude of 3450 m. Identical studies were also conducted in LLR acclimatized to HA (LLR-accl), high altitude natives (HAN) and in patients of AMS and HAPE. RESULTS: In LLR at SL, the mean +/- SD EPO levels were 8.93 +/- 3.75 mU x ml(-1), increased significantly after 8 h (20.0 +/- 11.06) of arrival at HA, peaked by day 1 (27.91 +/- 10.74 mU x ml(-1)), and started declining thereafter. The hemoglobin and hematocrit also increased after 8 h of arrival at HA and the increased levels were maintained during sojourn at high altitude. The EPO levels in LLR-accl were found to be significantly higher than the LLR SL values, but were not significantly different in HAN. The EPO levels in patients of AMS were not significantly different than the LLR values during the initial 2 d after arrival at HA but were found to be increased in patients of HAPE. CONCLUSION: Short or prolonged residency at HA is associated with increased secretion of EPO. The EPO response to hypoxia is not significantly altered in AMS but is markedly enhanced in HAPE, which may be due to exaggerated hypoxemia in these patients.     

Neurological conditions at altitude that fall outside the usual definition of altitude sickness

Altitude sickness in its commonly recognized forms consists of acute mountain sickness and the two life-threatening forms, high altitude cerebral and pulmonary edema. Less well known are other conditions, chiefly neurological, that may arise completely outside the usual definition of altitude sickness. These, often focal, neurological conditions are important to recognize so that they do not become categorized as altitude sickness because, besides oxygen and descent, treatment may be vastly different. Transient ischemic attacks, cerebral venous thrombosis, seizures, syncope, double vision, and scotomas are some of the well-documented neurological disturbances at high altitude discussed here in order to enhance their recognition and treatment.     

No association between high-altitude tolerance and the ACE I/D gene polymorphism

PURPOSE: The absence (deletion allele [D]) of a 287 base-pair fragment in the ACE gene is associated with higher ACE tissue activity than its presence (insertion allele [I]) and, as such, may enhance vasoconstriction and fluid retention through increased levels of angiotensin II and aldosterone. Because fluid retention is found in acute mountain sickness (AMS) and exaggerated pulmonary hypertension is essential in the pathophysiology of high-altitude pulmonary edema (HAPE), we hypothesized that the DD genotype is associated with increased susceptibility to these illnesses. METHODS: ACE genotype was thus determined in 83 mountaineers staying over night at 4559 m and related to AMS symptoms. Genotype was similarly determined in 76 mountaineers who had participated in previous studies at 4559 m; 38 of the latter group had a history of HAPE, and 25 had developed HAPE again during these studies. RESULTS: The allele frequency was in Hardy-Weinberg equilibrium in both investigations. Neither the history nor the observed episodes of HAPE nor the prevalence of AMS defined as an AMS-C score >/= 0.70 (environmental symptom questionnaire) in the first study or in both studies taken together were significantly different between the genotypes DD, ID, and II. CONCLUSION: We conclude that I/D-ACE gene polymorphism has no important effect on susceptibility to AMS or HAPE.     

关于高原病的命名、临床分型和诊断标准的建议

本文阐述了高原病的定义、命名、临床分型和诊断标准。强调指出高原病的命名和临床分型应根据临床特征并结合病因、病理生理、病理诸因素综合考虑,应力求精简,明确和实用,有利于临床诊断、治疗、预后判断和研究以及疾病统计管理,并对命名、分(?)和诊断标准作了简要讨论。     

高原病临床分型探讨

本文依据高原病发病原因、临床表现、发病的急缓和病程的长短及预后提出高原病的临床分型。认为本分型意见有利于临床诊断、疗效和预后判断,以及疾病统计管理等。并对疾病的分期作了阐述。     

速尿卡托普利治疗高原肺水肿患者的临床研究

目的：评价速尿、卡托普利对高原肺水肿（HAPE）的临床疗效。方法：采用右心漂浮导管的研究方法，观察了应用速尿、卡托普利对患者血流动力学的影响，同时采用Lake louise评分法对患者的病情进行定量评估。结果：速尿能明显降低HAPE患者的肺动脉压，而体动脉血压、心输出量、心率等血流动力学指标用药前后相比无明显变化。应用速尿后，HAPE患者的病情定量分数亦明显低于用药前；卡托普利虽然也能降低HAPE患者的肺动脉压，但无统计学意义，而患者的体循环平均压在用药后显著下降，患者的病情分数也未见明显改善。结论：速尿能明显改善HAPE的临床症状，且有选择性地降低HAPE患者肺动脉高压的作用。     

Who should not go high: chronic disease and work at altitude during construction of the Qinghai-Tibet railroad

From 2001 to 2005, a new railroad linking Beijing with Lhasa was built by more than 100,000 workers, of whom 80% traveled from their lowland habitat to altitudes up to 5000 m to work on the railroad. We report on the medical conditions of 14,050 of these altitude workers, specifically with regard to preexisting illness. All subjects were seen at low and high altitude. Average age was 29.5 +/- 7.4 (SD) yr, range 20 to 62 yr; 98.8% of the subjects were men and 1.2% were women. Overall incidence of AMS upon first-time exposure was 51%, that of HACE 0.28%, and that of HAPE 0.49%. About 1% of the subjects were hypertensive before altitude exposure. Those with blood pressure >or=160/95 were excluded from employment at altitude. Altitude exposure led to a greater increase of blood pressure in hypertensives compared to normotensives. On prealtitude screening prevalence of cardiac arrhythmias was 0.33%. Since the majority of these were rather benign and occurring in young and otherwise healthy subjects, we allowed altitude employment. Follow-up at altitude was uneventful. Subjects with coronary heart disease and diabetes were excluded from altitude employment. Obesity was a risk factor for acute mountain sickness and for reduced work performance at altitude. Overweight subjects lost more weight during their altitude stay than subjects with normal weight. Altitude exposure was a risk factor for upper gastrointestinal tract bleeding, especially in combination with alcohol, aspirin, and dexamethasone intake. Asthmatic subjects generally did better at altitude compared to low altitude, with the exception of one subject who experienced an asthma episode from pollen exposure. In conclusion, careful evaluation of preexisting chronic illness and risk factors allowed prevention of altitude deterioration of a preexisting health condition, all the while allowing subjects with some specific conditions to work and live at altitude without problems.     

Irregular nocturnal breathing patterns high altitude in subjects susceptible to high-altitude pulmonary edema (HAPE): a preliminary study

We studied nocturnal breathing patterns and symptoms of acute mountain sickness (AMS) during trekking in the Japanese Alps (altitude: 2,760-2,920 m) for 4 d in five subjects susceptible to high-altitude pulmonary edema (HAPE-S-S) and five control volunteers. Breathing patterns were evaluated with the impedance plethysmograph, and symptoms of AMS were evaluated by the environmental symptoms questionnaire-III score for AMS of cerebral type (AMS-C score). In both groups, the percentage of time with periodic breathing significantly increased at high altitude and the percentage in controls was significantly higher than in HAPE-S-S on the second night. In four HAPE-S-S, other disordered breathing patterns, termed "irregular breathing," were observed frequently by night at high altitude. Irregular breathing patterns were characterized by irregularly repeated oscillatory or nonoscillatory clusters of breaths with augmented tidal volume, followed by expiratory pause, apnea, or hypoventilation of various durations. All controls did not show significant changes in AMS-C score, but four HAPE-S-S showed the increase in AMS-C score on the next morning after frequent irregular nocturnal breathing. There was significant correlation between the percentage of time with irregular nocturnal breathing and AMS-C score on the next morning. These results suggest that HAPE-S-S are prone to irregular nocturnal breathing patterns at high altitude, which is associated with the development of AMS, but it was not possible to determine whether these abnormal breathing patterns are a cause or an effect of AMS.     

高原肺水肿治疗前后血清心肌肌钙蛋白T的变化

目的 探讨诊断和判别高原肺水肿（ＨＡＰＥ）状态的新指标。方法 在海拔３７００ｍ处对８例ＨＡＰＥ患者在治疗前及临床治愈后分别测定血清肌酸激酶同功酶（ＣＫ－ＭＢ）和ｃＴｎＴ两项指标。结果 ＨＡＰＥ患者血清ＣＫ－ＭＢ和ｃＴｎＴ临床治愈后较治疗前均降低,二者间的差别有非常显著性意义（Ｐ〈０．０１）。结论 ＨＡＰＥ时存在心肌损伤,血清ｃＴｎＴ是一项具有高灵敏度、高特异性的血清心肌损伤标志物,对ＨＡＰＥ的诊断、病情分析有一定的价值。     

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.     

高原肺水肿患者再缺氧损伤的观察

目的 评价氧疗在高原肺水肿治疗中的作用。方法 采用右心漂浮导管检测法，观察了8例高原肺水肿患者吸人纯氧及突然停止吸氧对患者肺动脉的影响，同时采用Lake Louise评分法对患者的病情进行定量评估。结果 高原肺水肿患者肺动脉平均压在吸氧1min后逐渐明显下降，患者在突然停止吸氧而改吸室内空气后，下降的肺动脉压逐渐回升，10min后回复到吸氧前水平，但随着时间的延长，肺动脉压继续攀升，20min后肺动脉压已明显高于吸氧前水平，25min后肺动脉压达最高值，与此同时，高原肺水肿患者病情定量分数亦显著高于吸氧前。结论高原肺水肿患者存在着再缺氧损伤，而肺动脉压异常升高在其发生中起重要作用。     

高原肺水肿的X线表现征象与发病时间和病理的关系

目的:分析35例高原肺水肿的X线表现征象,讨论与不同发病时间及病理改变的关系和意义。方法:西藏昌都地区平均海拔高度3 500m,昌都邦达机场平均海拔高度4 600m。35例中除1例外籍人士外均为汉族,第一次急进高原23例,再次重返高原12例。乘飞机首次抵海拔4 600m高原后不久发病16例,而再次重返高原中有3例。结果:高原肺水肿早期(发病第1天)X线表现征象:以肺纹理增多似间质型纤维化或支气管炎样改变、小斑片影或似絮状影改变为主,以右肺中下叶改变多;进展期(第2天~3天)呈多样特点,如小斑片影似絮状影、斑片影似有融合样改变、片影如蝶翼样其典型为蝴蝶状分布于两肺、弥漫状实变影;稳定期与恢复期(第4天~5天)与早期似有一定类似,如以小斑片影或似絮状影改变,肺纹理增多似间质型纤维化与支气管炎样改变为主。结论:高原肺水肿系综合因素结果,除低氧刺激使肺泡壁内毛细管超微结构改变与神经、体液调节紊乱外,高寒低温、上呼吸道感染与休息不佳等均有明显关系,高原肺水肿的X线表现不但与发病的时间有明显关系,也与病理改变联系密切。