野外與登山醫學---2013 NEJM HAI 高海拔疾病 guideline 2013-07-13

Acute High-Altitude Illnesses 這篇研究是在 2013 年刊登於 NEJM 的. 

作者 Peter Bärtsch, M.D., and Erik R. Swenson, M.D. 

 N Engl J Med 2013; 368:2294-2302June 13, 2013DOI: 10.1056/NEJMcp1214870

統一名詞翻譯

HAI 高海拔疾病 high altitude illness 
AMS 急性高山病(最好不要翻譯成急性高山症) (與他人溝通時-直接講AMS比較明確)
HACE 高海拔腦水腫 high altitude cerebral edema
HAPE 高海拔肺水腫 high altitude pulmonary edema
acetazolamide 下面都以"丹木斯" 代替 (學名不容易記.,且中文翻譯也不一致)

dexamethasone 下面以類固醇代替 (類固醇有很多種類. 並非只有這種)
(在高海拔疾病研究 . dexamethasone 相關研究最多)

重點整理
AMS主要危險因子包括: 
1. 曾經罹患高山症,
2. 海拔2000公尺以上, 一天上升超過 625公尺,
3. 沒有做高度適應(在最近兩個月,於高度3000公尺以上環境,待超過五天)
AMS次要危險因子包括
4. 女性
5. 46歲以下 (腦部相對萎縮,能代償腦部水腫)
6. 有偏頭痛病史 (比較容易頭痛)

體能鍛鍊無法降低高海拔疾病風險(但鍛鍊體能還是登山必要的準備)

運動會讓AMS症狀惡化

同一海拔前三天沒事, 第四天開始出現AMS症狀, 要考慮其他原因(不像AMS)

HACE  (腦水腫)通常發生在海拔 4000 公尺以上(低海拔也有案例)
HAPE  (肺水腫)通常發生在海拔 3000 公尺以上(低海拔也有案例)

使用Lake Louise Score 評估AMS, 建議在抵達六小時(維持相同海拔)之後再評估 (以減少因為脫水, 體力不濟等等因素的干擾)

預防高海拔疾病最好的方式還是緩慢提升海拔高度, 當行程無法修改. 只好藉助藥物來降低發生機率. 

(下面是文章開始了)

臨床問題
一開始文章開頭問了一個有趣的問題
45歲健康男性，想花五天時間攀登吉立馬札羅山(5895公尺)，從海拔 1800 公尺開始攀登，最近的體能測驗是正常的，他每一週跑10公里四到五次，去年花了不到四小時完成馬拉松，他想知道如何在高海拔避免生病，是否上山前幾週進行常壓低氧環境的訓練或睡眠會有幫忙，你的建議呢？

A 45-year-old healthy man wishes to climb Mount Kilimanjaro (5895 m) in a 5-day
period, starting at 1800 m. The results of a recent exercise stress test were normal; he runs 10 km 4 or 5 times per week and finished a marathon in less than 4 hours last year. He wants to know how he can prevent becoming ill at high altitude and whether training or sleeping under normobaric hypoxic conditions in the weeks before the ascent would be helpful. What would you advise?
＊－。－。－。－。－。－。－。－－。－。－。－。－＊
在低氧常壓的環境做訓練或睡覺, 是否能避免高山症發生?
傳統上, 海拔超過 2500 公尺的環境會引起高海拔疾病, 但少數人因為體質關係, 可能在 2000-2500 公尺的高度就出現高海拔疾病症狀。

AMS 急性高山病
隨著海拔上升引起的頭痛是AMS急性高山病主要症狀, 會伴隨食慾不振、噁心、疲憊、頭暈、倦怠、失眠等症狀。AMS 通常在上升到海拔2500公尺以上, 6-12小時之後發生。海拔越高，嚴重度及盛行率越高。沒有做高度適應的人，海拔2500公尺發生率 10-25%, 但症狀通常輕微，在海拔4500-5500公尺發生率50-85%. 且可能病倒。
在一個回溯性研究, 發現下列三項主要危險因子, 另一個對於海拔4000-8848公尺的健行者和登山客的前瞻性研究發現, 有相似的危險因子
AMS主要的危險因子
1. 曾經罹患高山症,
2. 海拔2000公尺以上, 一天上升超過 625公尺,
3. 沒有做高度適應(在最近兩個月,於高度3000公尺以上環境,待超過五天)
次要危險因子:
4. 女性
5. 46歲以下 (腦部相對萎縮,能代償腦部水腫)
6. 有偏頭痛病史 (比較容易頭痛)

在高海拔地區進行運動可能會讓AMS急性高山病惡化, 但良好的體適能並沒有保護效果. (體力好的人一樣可能得到AMS急性高山病).
適當處置之後通常1-2天症狀會改善 (如果症狀太多天, 考慮其他診斷)

HACE, HAPE 患者都可能會發燒. 不能用發燒來排除高海拔疾病(低海拔, 發燒最常見原因是感染症)

HACE 高海拔腦水腫(high altitude cerebral edema) HACE 是 AMS 末期表現, 可視為同一種疾病.
HACE特徵是軀幹運動失調 truncal ataxia, 神智變差, 通常會輕微發燒 (所以發燒無法排除腦水腫或肺水腫)
如果沒有治療會快速昏迷, 24小時內因為腦部疝氣造成腦死. (腦水腫沒有黃金時間. 隨時會死亡. 應立即下降高度, 切勿原地待援)

對於一般止痛藥物(NSAID非類固醇消炎止痛藥)反應不佳的頭痛及嘔吐代表病患可能由AMS正在惡化. 往 HACE 進展
但沒有頭痛或其他AMS症狀也不能直接排除HACE (HAPE造成的缺氧, 症狀會與 HACE 相似, 無法區別, 故只能當成同時罹患 HACE 同時治療)
HACE通常發生於海拔 4000公尺以上, 至少停留兩天以上的時間, 在海拔4000公尺至5000公尺的盛行率約0.5~1%, MRI可以發現血管性腦水腫, 主要在胼胝體 corpus callosum 部位出現微量出血.

HAPE 高海拔肺水腫
HAPE特徵: 沒有精力、呼吸困難、運動時乾咳、之後出現休息時呼吸困難、呼吸有囉音、發紺、咳嗽、粉紅色泡沫痰。
氣體交換狀況惡化也會增加得到HACE的危險，這種狀況通常在海拔超過3000公尺之後的兩天發生，在海拔2500-3000公尺比較少見。

HAPE的危險隨著高度以及上升速度增加，例如，如果不知道過去的疾病史，在四天時間上升超過海拔4500公尺以上, 得到HAPE的機率是 0.2%, 如果是七天時間上升至海拔5500公尺, 得到HAPE的機率是 2%, 如果在一兩天之內到達上述海拔，機率各增加為 6%, 15%.
(所以上升到同樣高度，花的時間越短，得到HAPE機率越大，從 0.2%變成 6%，2% 變成 15%)

如果之前曾經得到HAPE, 再次得到的機會越大，在兩天時間上升至海拔4500公尺, 得到HAPE的機率是 60% (一般人6%)

沒有治療的HAPE, 死亡率約 50%.
HAPE是非心因性的肺水腫, 起因於低血氧造成的肺血管收縮. 以及異常的肺動脈高壓, 微血管壓力上升. 這種異常的高壓造成非發炎性及出血性的肺泡滲漏, 之後可能再引起續發性的發炎反應。
(白話文: 一開始是因為血管內壓力大, 造成血管內的液體往外漏到肺泡, 正常肺泡內不應該有液體, 這種狀況一開始是物理性反應, 並不是發炎(化學性)反應, 但之後可能因為肺泡內有液體而造成後續有發炎發應)

The Clinical Problem
Persons who are not acclimatized and ascend rapidly to high altitudes are at risk for any of several debilitating and potentially lethal illnesses (Table 1) that occur with-in the first days after arrival at high altitudes. Traditionally, 2500 m has been used as the threshold for high-altitude illnesses; in rare cases, mild illness occurs in persons who have ascended above 2000 m but below 2500 m.

Acute Mountain Sickness
Headache that occurs with an increase in altitude is the cardinal symptom of acute mountain sickness and is usually accompanied by anorexia, nausea, dizziness, malaise, sleep disturbance, or a combination of these symptoms. Acute mountain sickness generally occurs within 6 to 12 hours after a person ascends to 2500 m or higher. Its prevalence and severity increase with increasing altitude. Acute moun-tain sickness occurs in approximately 10 to 25% of unacclimatized persons who ascend to 2500 m. Symptoms are usually mild at this altitude and have little effect on activity. However, acute mountain sickness occurs in 50 to 85% of unacclimatized persons at 4500 to 5500 m and may be incapacitating.

In a retrospective study, major independent risk factors for acute mountain sick-ness included a history of acute mountain sickness, fast ascent (≥625 m per day above 2000 m), and lack of previous acclimatization (A prospective study involving trekkers and climbers who went to altitudes between 4000 and 8848 m showed the same major risk factors for incapacitating acute mountain sickness and other severe altitude illnesses (described below). Other possible risk factors include female sex, an age younger than 46 years, and a history of migraine. Exercise may exacerbate acute mountain sickness, but good physical fitness is not protective. Symptoms usually resolve within 1 to 2 days when appropriate measures are taken (see below).

High-Altitude Cerebral Edema
High-altitude cerebral edema is characterized by truncal ataxia, decreased con-sciousness, and usually mild fever.
Without appropriate treatment, coma may evolve rapidly, followed by death from brain herniation within 24 hours. Headache that is poorly responsive to nonsteroidal anti-inflammatory drugs (NSAIDs) and vomiting indicate probable progression of acute mountain sickness to high-altitude cerebral edema, but the absence of headache and other symptoms of acute mountain sickness does not rule it out.
High-altitude cerebral edema usually develops after at least 2 days at altitudes above 4000 m. The prevalence is estimated to be 0.5 to 1.0% among persons at 4000 to 5000 m. Magnetic resonance imaging in patients with high-altitude cerebral edema shows vasogenic edema and microhemorrhages that are located predominantly in the corpus callosum.

High-Altitude Pulmonary Edema
High-altitude pulmonary edema is characterized by loss of stamina, dyspnea, and dry cough with exertion, followed by dyspnea at rest, rales, cyanosis, cough, and pink, frothy sputum. Deterioration in gas exchange also increases the risk of high-altitude cerebral edema. This condition develops 2 or more days after exposure to altitudes above 3000 m and is rare in persons at altitudes below 2500 to 3000 m. The risk increases with increased altitude and faster ascent. For example, the incidence among persons with an unknown history of high-altitude pulmonary edema is 0.2% if they ascend to 4500 m in 4 days and 2% if they ascend to 5500 m in 7 days; the incidence increases to 6% and 15%, respectively, when these altitudes are reached within 1 to 2 days.
The risk is further increased among persons with a history of high-altitude pulmonary edema (e.g., the risk of recurrence is 60% among persons who ascend to 4500 m in 2 days). The estimated mortality among persons with untreated high-altitude pulmonary edema is 50%. This disorder is a noncardiogenic pulmonary edema caused by exaggerated hypoxic pulmonary vasoconstriction and abnormally high pulmonary-artery pressure and capillary pressure.

These high pressures lead to a noninflammatory and hemorrhagic al-veolar capillary leak that secondarily may evoke
an inflammatory response.

策略及證據 Strategies and Evidence
風險評估
在高海拔停留時, 要針對可能在高海拔惡化的心肺疾病做臨床評估，雖然在這篇文章，並非討論個人疾病受到高海拔的影響，不過有一些回顧性的文章可以參考。
過去如果曾經得到高海拔疾病, 再發的可能性會上升, 過去病患曾經在高海拔的經歷, 先前登高的適應狀況, 攀登及睡覺的最高海拔, 上升速率, 以及任何高海拔疾病都要詳細了解, 此次風險的評估, 以過去相似海拔的上升速率最高海拔做參考比較可靠.
Risk Assessment
Risk assessment (Table 2) should start with a clinical evaluation directed toward any cardiopulmonary diseases that might worsen during a sojourn involving high altitude. Although a discussion of the effect of altitude in persons with preexisting disease is not within the scope of this article, reviews of this topic are available.
Given that previous altitude illness is a strong predictor of recurrence, detailed information about the person’s history with respect to visits to high-altitude areas, acclimatization before previous ascents, maximum altitudes for climbing and sleeping, rates of ascent, and any altitude illness should be obtained. The estimation of risk is most reliable for persons with previous rates of ascent and final altitudes that were similar to those planned.

其他評估
曾有報告提出, 休息時及運動時, 由缺氧狀態引發的換氣反應, 曾被假定為預測發生高海拔疾病風險的工具

容易罹患高海拔疾病的病人, 在氧氣濃度 11.5% 的環境休息或運動時增加的換氣量, 在 3000 公尺海拔經過 30 分鐘後的動脈氧氣濃度, 或相應的常壓低氧的環境, 其數值會比常人低. (換氣量低，氧氣濃度低)

不過在一篇回溯性研究發現, 容易得高海拔疾病與不易得高海拔疾病的兩組人, 會有顯著重疊的現象,
另一篇前瞻性研究發現, 容易得到 AMS 的一組, 與不容易得病的一組, 也是有重疊現象
所以無法訂出一個絕對的數值, 來推測登山者是否容易或不容易得到高海拔疾病.

一篇關於嚴重高海拔疾病的危險因子的多變項分析指出, 依照個人的體質及疾病史 (性別、體能、上升速率、先前得到嚴重高海拔疾病及偏頭痛的狀態) 得到的推測, 如果加上使用其他數據, 像是低氧的通氣量反應, 其他低氧環境的生理數值, 也無助於評估是否容易得到高海拔疾病.

曾經罹患兩次 HAPE 的登山者, 容易再罹患 HAPE, 這類病患在低氧環境 (海平面壓力12%氧氣濃度) 的肺動脈壓力會異常上升 (大於40 mmHg)
一篇西歐人種的研究指出, 10% 的人在低血氧時肺動脈壓力會增高, 但在這群肺動脈高的人在快速上升後, 只有 15% 會得到HAPE. 而HAPE測試前的可能性本來就低(在聖母峰基地營的健行者約1-2%), 因此在低氧環境測量肺動脈壓力, 也無法預估病患是否容易得到HAPE.

雖然運動員比一般人容易登頂, 但體適能與是否容易得到 AMS 或 HAPE 無關,
因此, 運動(體能)測試無法用來評估登山者是否容易發生高海拔疾病,

平時常規的運動量和運動強度, 以及體適能表現, 有助於評估是否有足夠的儲備能力以應付高海拔造成的體力下降
(超過1500公尺海拔, 每上升 100 公尺約下降 1%).
平時沒有訓練體力的人, 建議在開始攀登前的數星期到數個月, 尤其是預期在高海拔進行嚴酷的戶外活動時, 應進行常規體能訓練.

Other Assessments
The assessment of ventilation in response to exposure to hypoxic conditions at rest or during exercise has been proposed as a means of refining risk prediction for altitude sickness. The increase in ventilation at rest or during exercise while breathing 11.5% oxygen, as well as arterial oxygen saturation after the first 30 minutes of exposure to an altitude of 3000 m or to corresponding normobaric hypoxic conditions, is on average significantly lower in persons who are susceptible to acute altitude sickness than in those who are not.

However, considerable overlap between groups classified as susceptible and those classified as not susceptible in a retrospective study and between a group classified as having acute mountain sickness and a group classified as unaffected in a prospective study makes it impossible to define cutoff values that are sufficiently sensitive and specific to be useful in practice. A multivariate analysis of risk factors for severe high-altitude illness showed that the hypoxic ventilatory response and other physiological measurements under hypoxic conditions add little to the discrimination provided by patient characteristics and history (i.e., sex, level of physical activity, rate of previous ascent, and status with respect to previous severe high-altitude illness and migraines). Persons who are considered to be susceptible to high-altitude pulmonary edema because of two previous episodes of high-altitude pulmonary edema have abnormally high systolic pulmonary-artery pressure (>40 mm Hg) under hypoxic conditions (12% oxygen in ambient air at sea level). In a study of a western European population, exaggerated hypoxic pulmonary-artery pressure was detected in about 10% of study participants, but high-altitude pulmonary edema develops in only 15% of persons with exaggerated hypoxic pulmonary-artery pressure responses who make a rapid ascent (unpublished data). For this reason and because of a very low pretest probability of high-altitude pulmonary edema (e.g., an incidence of 1 to 2% among trekkers to the Mount Everest base camp), measurement of pulmonary-artery pressure under hypoxic conditions cannot be recommended as a means of identifying persons who are susceptible to high-altitude pulmonary edema. Although athletic persons are more likely to reach the summit than persons who are not athletic, physical fitness appears to have no association or at most a modest association with susceptibility to acute mountain sickness and high-altitude pulmonary edema. Thus, an exercise test is not indicated to assess the risk of acute high-altitude illness. Information about the amount and intensity of the person’s regular exercise as well as his or her level of athletic performance is helpful in estimating whether there is sufficient reserve to cope with the expected loss of exercise capacity at high altitudes of about 1% for every 100 m above 1500 m. Persons without athletic training should be encouraged to begin regular physical exercise several weeks to months before the planned ascent, particularly when rigorous outdoor activities are planned at high altitudes.

table 2 (所有海拔高度都是指睡覺的海拔)

攀登玉山，第一天住排雲山莊，海拔 3402 公尺，第二天清晨三點開始爬山，上升到玉山 3952 公尺再下山。
1. 快速上升，第一天住宿時就上升 3402 公尺。
2. 第二天一樣是快速上升，海拔三千公尺以上，一天上升 500 公尺。
所以至少是中度以上風險。

~~~低風險:
上升速率慢 (海拔2500公尺以上,每天上升500公尺以下). 過去在相同海拔沒有AMD、HACE、HAPE; 已經稍微適應的登山者, 快速上升 (海拔2500公尺以上, 每天上升超過 500 公尺) (在未來幾星期, 停留在海拔 3000 公尺以下)
Slow ascent (≤500 m/day above 2500 m); no history of acute mountain sickness, high-altitude cerebral edema, or high-altitude pulmonary edema with previous exposure to similar altitude; rapid ascent (>500 m/day above 2500 m) for persons who are partially acclimatized (exposure to high altitudes of

~~~中度風險:
不知道是否曾有AMS, HACE, HAPE的病史, 快速上升(海拔3000公尺以上, 每天上升大於 500 公尺
不知道是否AMS, 快速上升 (一天上升到海拔 3000 公尺以上)
(台灣高山的登山口有些海拔就超過 3000公尺了, 所以從平地開車上去, 第一天海拔就破表 )
Unknown history of acute mountain sickness, high-altitude cerebral edema, or high-altitude pulmonary edema and fast ascent (>500 m/day above 3000 m); unknown history of acute mountain sickness and rapid ascent (ascent to >3000 m in 1 day)

~~~高度風險:
不知道是否曾有AMS, HACE, HAPE的病史,非常快速上升(通常指一天超過500公尺).最後停留在海拔超過4000公尺.
過去在相同海拔曾經有AMS, HACE, HAPE(與此次計畫要攀登的海拔相似)
Unknown history of acute mountain sickness, high-altitude cerebral edema, or high-altitude pulmonary edema, very rapid ascent (considerably >500 m/day), and high final altitude (>4000 m); history of acute mountain sickness, high-altitude cerebral edema, or high-altitude pulmonary edema with previous exposure to high altitude that is similar to the planned ascent


Table 3. Prevention of High-Altitude Illnesses. 預防高海拔疾病

在暴露前先適應: 先到中等海拔, 2000公尺以上海拔待幾天, 或到 3000公尺以上海拔健行或攀登一天(當天下來).
慢慢上升: 海拔 2500~3000 公尺, 每天上升 300~500公尺, 每三四天休息一天, 適當的治療高海拔疾病早期症狀, 以避免嚴重高海拔疾病.

預防AMS, HACE的藥物
中度風險: ACETAZOLAMIDE 半顆 125mg, 早晚各一次 (一天一顆分兩次吃), 如果副作用強, 或者有禁忌症無法吃 ACETAZOLAMIDE, 改成吃 DEXAMETHASONE 早晚各 4mg.
高度風險: 每次一顆ACETAZOLAMIDE, 一天吃兩次到三次(一天兩次, 中間間隔8-12小時; 一天三次, 中間間隔 4-8 小時), 或 DEXAMETHASONE 每次 4mg 一天三次.

預防HAPE藥物
第一線: NIFEDIPINE 30mg 緩慢釋放劑型, 每天兩次(8-12小時一次)
第二線: PD5抑制劑(例如 tadalafil 犀利士一天一顆分兩次吃, 每次半顆10mg, 8-12小時吃一次) 或 DEXAMETHASONE 每次 8mg, 一天兩次(8-12小時吃一次).
第三線: 吸入型SALMETEROL (每次125ug每天兩次)效果比要差, 副作用在某些人會出現顫抖, 心跳快.




Method ~~~~~~~~~~~~~~~~~~~~~~~~~~~~Description
Acclimatization before exposure ~~~~~~~~~Sojourning several days at intermediate altitudes at or above 2000 m (staging), hiking or climbing on day tours above 3000 m, or both


Slow ascent ~~~~~~~~~~~~~~~~~~~~~~~~ Ascent rate of 300–500 m/day above 2500–3000 m, with a day of rest every 3–4 days; appropriate treatment of early symptoms of acute mountain sickness for prevention of severe high-altitude disease




Drugs for prevention of acute mountain sickness,high-altitude cerebral edema, or both


Moderate risk ~~~~~~~~~~~~~~ Acetazolamide, 125 mg twice/day; if there are side effects with or contraindications to acetazolamide, dexamethasone, 4 mg twice/day, can be used


High risk Acetazolamide, 250 mg two or three times/day (three times/day recommended for rapid ascent, though efficacy uncertain); dexamethasone, 4 mg three times/day, if acetazolamide has unacceptable side effects or is contraindicated


Drugs for prevention of high-altitude pulmonary edema in persons with history of this condition
First line ~~~~~~~~~~~~~~~ Nifedipine, 30 mg of slow-release formulation twice/day
Second line~~~~~~~~~~~~~ Phosphodiesterase-5 inhibitors (e.g., tadalafil, 10 mg twice/day) or dexamethasone, 8 mg twice/day
Third line~~~~~~~~~~~~~~~ Inhaled salmeterol (125 μg twice/day) appears to be less effective than other options and may cause tremor and tachycardia in some persons with this dose

CLINICAL KEY POINT 臨床關鍵重點
高海拔疾病發生於海拔2500公尺以上的頭幾天, 無法適應高度的人, 依據個人體質及過去病史會有很大的差異性.
頭痛是AMS主要症狀, 如果AMS沒有好好治療, 會進展成危及生命的HACE或HAPE (這句話很怪, 因為AMS/HACE. 與 HAPE 其實是兩種不同生理病理反應. 不同疾病. HAPE 病患與AMS病患雖然重疊部分很高. 但可單獨出現. )
高海拔疾病能夠藉由控制上升速度來避免(海拔3000公尺以上, 每天300-500公尺, 每3-4天要有一個休息天)

使用acetazolamide 或 dexamethasone 可以降低AMS或HACE的機率.
使用nifedipine、phosphodiesterase-5 inhibitors(威而鋼、犀利士)、dexamethasone,可以降低HAPE的機率

AMS的頭痛可使用NSAID或休息來治療, 但嚴重的狀況應該下降或給氧氣, 嚴重的AMS或HACE可使用dexamethasone。HAPE可以使用 nifedipine或 phosphodiesterase-5 inhibitors來治療, 治療過後應該盡可能立即下降. (藥物可以爭取時間, 但並非絕對安全, 治療結果不一定能好轉, 及早下降)

註解:
AMS 急性高山症 acute mountain sickness
HACE 高海拔腦水腫 high altitude cerebral edema
HAPE 高海拔肺水腫 high altitude pulmonary edema
NSAID 非類固醇消炎止痛藥 (電視廣告的肌立即屬於此類)
phosphodiesterase-5 inhibitors =PDE5抑制劑, 如威而剛、樂威壯、犀利士

acetazolamide 乙酰唑胺片, 以前大家比較知道的是DIAMOX丹木斯, 不過丹木斯2006年停產, 目前台灣可以買到同成分的藥物
dexamethasone 類固醇 http://tinyurl.com/n8j2hey
nifedipine 降血壓藥物, 屬於鈣離子阻斷劑, 內科醫師常用於突發性血壓升高 http://tinyurl.com/mtrxcdp(但不建議血壓突然升高的患者直接使用nifedipine)


Acute High-Altitude Illnesses
• Acute high-altitude illnesses occur in persons who are not acclimatized during the first days at an altitude of 2500 m or higher, with wide variation in the incidence according to patient characteristics and history.
• Headache is the major symptom of acute mountain sickness. If acute mountain sickness is not treated adequately, it can progress to life-threatening high-altitude cerebral or pulmonary edema.
• High-altitude illnesses can be prevented by ascending 300 to 500 m per day at altitudes above 3000 m and including a rest day every 3 to 4 days.
• Risks of acute mountain sickness and high-altitude cerebral edema are reduced with the use of acet-azolamide or dexamethasone; the risk of high-altitude pulmonary edema is reduced with the use of nifedipine, phosphodiesterase-5 inhibitors, or dexamethasone.
• Acute mountain sickness may be treated by a day of rest and nonsteroidal antiinflammatory drugs for headache, but when it is severe, descent or supplemental oxygen is indicated. Dexamethasone is indi-cated for severe acute mountain sickness or high-altitude cerebral edema, and nifedipine or phospho-diesterase-5 inhibitors are indicated for high-altitude pulmonary edema; treatment with these agents should be followed by descent as soon as possible.

預防
非藥物方式 雖然系統性評估上升速率(指連續兩晚睡眠海拔的增加)對於預防高海拔疾病的影響, 缺乏前瞻性研究的數據, 海拔3000公尺以上的攀登指引建議每天上升速率 300-500 公尺, 每 3-4 天應該休息一天. (請看table 3). 對於不同攀登者, 攀登速率與結果存在著很大的差異, 沒有高海拔攀登經驗的登山者建議遵照此指引, 如果預計的攀登速率更快, 其他的方式, 例如攀登前的適應策略, 或用藥物預防. 登山者或者高地居民在3000公尺海拔進行體能訓練數星期, 接著攀登 4500 公尺以上海拔, 發生AMS的機率會比較低(不受個人體質與上升速率影響). 在海拔 2000 公尺以上停留一星期之後, 與海平面做比較, 攀登4500 公尺海拔的AMS發生率以及嚴重度會下降 50%. 曾有人假設, 攀登前暴露於相當於海拔 2500-3000 公尺的常壓低氧的環境, 可能對有預防AMS的效果, 在一個雙盲試驗發現, 重複間隔性暴露在相當於海拔2500-4500公尺的常壓低氧環境 60-90 分鐘, 或持續在相當於 2500-4500 公尺海拔的常壓低氧狀態睡 8 小時, 連續七天, 對於降低4300~4559公尺的AMS的機率和嚴重度沒有影響. 因此, 要降低高海拔疾病的風險, 建議待在海拔 2000-3000 公尺大約一星期, 以及在更高海拔從事日間健行或攀登, 且要在攀登前的時間做，因為不知道這種高度適應有效的時間能持續多久
Prevention Nonpharmacologic Approaches Although data are lacking from prospective studies that systematically assess the influence of the rate of ascent (defined as the gain in altitude between the altitudes at which one sleeps on 2 consecutive nights) on prevention of acute high-altitude illnesses, guidelines for ascents to altitudes above 3000 m recommend ascent rates of 300 to 500 m per day and a day of rest every 3 to 4 days (Table 3). However, there are large differences among persons with respect to ascent rates that are not associated with poor outcomes. A person without previous experience in high altitudes should follow the ascent rates recommended by these guidelines. If the planned ascent rate is faster, additional measures, such as acclimatization strategies before the ascent or prophylactic medications, should be considered. Mountaineering or residence with regular physical activity at altitudes above 3000 m in the weeks preceding a climb to 4500 m is associated with a reduced incidence of acute mountain sickness that is independent of the person’s susceptibility to this condition and the rate of ascent. An ascent made after 1 week at an altitude of 2000 m or higher, as compared with an ascent from near sea level, reduces both the incidence and severity of acute mountain sickness at 4300 m by 50%. It has been hypothesized that exposure to normobaric hypoxic conditions before an ascent might provide protection against acute mountain sickness. In double-blind, placebo-controlled trials, however, repeated intermittent exposure to normobaric hypoxia equivalent to an altitude of 2500 to 4500 m for 60 to 90 minutes or continuous exposure to normobaric hypoxia equivalent to an altitude of 2500 to 3000 m during 8 hours of sleep on 7 consecutive nights did not significantly reduce the incidence or severity of acute mountain sickness at altitudes of 4300 to 4559 m. On the basis of these data, a recommended strategy to reduce the risk of high-altitude illness is to remain at an altitude between 2000 and 3000 m for about a week and to include day hiking or climbing at higher altitudes. This should be done as close in time as possible to the trek or expedition, since it is not known how quickly acclimatization diminishes with time.
一項隨機性安慰劑對照的實驗指出，上升前一小時，服用 320mg 的水楊酸，吃三次，每次間隔四小時，或者上升前數小時吃 600mg 的 ibuprofen 一天三次，在攀登到 3480～4920 公尺海拔時，能顯著的降低頭痛的機率。 頭痛是 AMS 的定義症狀，在這些研究都發現能降低頭痛的機率，但只能維持一到兩天 (如果真的得到 AMS，吃止痛藥物無法真正治療 AMS，只能緩和症狀而已，所以當 AMS 變更嚴重，藥物就感覺沒效了) 吃止痛藥物(NSAID類)的風險是腸胃道出血，在高海拔發生機率會增加，但目前缺乏研究來評估這種風險。 當風險評估指出有高度可能性得到高山症 AMS，建議吃 acetazolamide。 在一個大型的前瞻性觀察性研究，使用 acetazolamide 能降低 44% 的嚴重高海拔疾病風險。 一個多變項分析研究指出，在上升前服用各種劑量的 acetazolamide，能明顯減少 AMS，作者總結，預防性的最低有效劑量是 125mg，一天兩次 (在台灣目前常用的劑量是一顆 125mg，等於一次半顆，一天早晚各吃一次，一天總共吃一顆) 一次 125mg 一天兩次的劑量能預防 1600 公尺海拔上升到 4300公尺海拔的高山症 AMS，或降低在 4200公尺沒有高山症的健行者，繼續上升至 4900 公尺海拔時的高山症 AMS 機率。 然而，另一項研究，使用每次 250mg，一天兩次的劑量，在吉立馬札羅山快速上升時(五天內上升到 5895 公尺海拔），發生高山症機率 50%，所以低劑量 acetazolamide 對於更快速的上升以及更高的海拔可能不夠。但更高劑量是否更有效果，目前仍不知道。 acetazolamide 需要在上升前一天開始服用，在最高海拔之後持續再吃兩天，或服用到下降為止。 一個多變項分析指出，服用 acetazolamide 的病人，35-90% 會出現手指頭麻木(感覺異常)，在前幾次服用時， 8-55% 會出現多尿的症狀。4-14% 在喝碳酸飲料時會出現味覺異常。在低海拔(表示非高山症)服用 acetazolamide 250mg 一天三次的人，20% 會出現噁心、疲倦的症狀。 因此，建議在上山前先服用 acetazolamide ，對於上山之後區分是藥物副作用，或者是得到高山症，會有幫忙
Prophylactic Medication
Randomized, placebo-controlled trials have shown a significant reduction in the risk of headache with the use of acetylsalicylic acid at a dose of 320 mg taken three times at 4-hour intervals, starting 1 hour before ascent, 31 or ibuprofen at a dose of 600 mg three times per day, 32,33 starting a few hours before ascent to altitudes between 3480 and 4920 m. Headache is a defining symptom of acute mountain sickness, and the incidence of this condition was reduced in all these trials, which lasted 1 or 2 days only. A risk associated with these medications is gastrointestinal bleeding, which may be increased at high altitudes, 34 but studies were not powered to assess this risk. When risk assessment indicates a high probability of the development of acute mountain sickness (Table 2), acetazolamide is recommended. In a large, prospective, observational study, the use of acetazolamide was associated with a 44% reduction in the risk of severe high-altitude illnesses. 7 A meta-analysis of randomized trials of various doses of acetazolamide initiated before ascent likewise showed a significantly reduced risk of acute mountain sickness; the authors of this meta-analysis concluded that the lowest effective dose for prevention is 125 mg twice per day. 35 This dose has been shown to be effective in reducing the incidence of acute mountain sickness associated with rapid ascent from a baseline altitude of 1600 to 4300 m 36 or during further ascent to 4900 m among trekkers who have ascended to 4200 m without illness. However, a study that showed acute mountain sickness in more than 50% of persons who received acetazolamide at a dose of 250 mg twice per day during a rapid ascent of Mount Kilimanjaro (5895 m in 5 days) 38 suggested that low-to-moderate doses may be inadequate with more rapid ascents and higher final altitudes; it is not known whether higher doses are more effective in persons at these altitudes. Acetazolamide should be started 1 day before the ascent and discontinued after 2 days at the final altitude or during the descent. A meta-analysis showed that acral paresthesias occurred in 35 to 90% of persons receiving acetazolamide, and polyuria occurred with the first several doses in 8 to 55%, with distaste for carbonated beverages in 4 to 14%. Nausea and tiredness developed in about 20% of persons who received 250 mg of acetazolamide three times per day at low altitudes. Thus, testing for side effects of the drug before the ascent might be useful to avoid confusion of a side effect with a symptom of acute mountain sickness. If side effects occur, the person should be advised not to use this prophylactic agent. If there is a contraindication to acetazolamide or if it has intolerable side effects, an alternative is dexamethasone at a dose of 4 mg two or three times per day. In a randomized, placebo-controlled trial, dexamethasone was associated with a significant reduction in the incidence and severity of acute mountain sickness among persons who ascended to 2700 m. 40 Several smaller randomized trials, including one head-to-head trial, have also shown these results at 4300 to 4570 m, with a magnitude of effect similar to that of acetazolamide. 10 Given the potential adverse effects of dexamethasone (e.g., hyperglycemia, adrenal suppression, and psychosis), its use for prevention of acute mountain sickness should be limited to persons with unequivocal indications, and it should be administered fo less than 1 week. Since there appears to be a continuum from acute mountain sickness to high-altitude cerebral edema, drugs that prevent the first condition will probably also reduce the risk of the second one. However, systematic data are lacking to confirm this theory.
高海拔肺水腫的預防 可以使用 nifedipine 每天兩次, 每次 30mg, Tadalafil 每天兩次, 每次 10mg 類固醇是可以用的，每天吃兩次 8mg dexamethasone 可以將HAPE發生率從 70% 降低至 10% 以下
高劑量吸入性氣管擴張劑 salmeterol 每天兩遍, 每一遍噴五下, 效果比較不好, 但在一篇研究報告指出, 可以將HAPE機率從 74% 降低到 33%
Small randomized trials involving persons with a history of high-altitude pulmonary edema have shown that the risk of recurrence can be reduced with the use of medications that lower the high pulmonary-artery pressure that is typical in susceptible persons. Nifedipine in a slow-release formulation at a dose of 30 mg twice perday, 41 tadalafil (a phosphodiesterase-5 inhibitor) at a dose of 10 mg twice per day, and dexamethasone at a dose of 8 mg twice per day 42 appear to be similarly effective in lowering pulmonaryartery pressure and reducing the incidence of high-altitude pulmonary edema from approximately 70% to approximately 10% or less. Although it has not been compared directly with these agents, inhaled salmeterol, a long-acting β 2 -agonist, at a high dose of 5 puffs (125 μg) twice per day, appears to be less effective; in a placebo-controlled trial, it was associated with a reduction in the incidence of high-altitude pulmonary edema from 74% to 33%.
治療 Treatment
通用處置: 下降, 給氧氣, 加壓艙
藥物


輕度至中度的AMS通常需要休息一天, 吃NSAID止痛, 或吃止吐藥物治療嘔吐, 吃IBUPROFEN 可以顯著降低頭痛症狀, 氧氣及丹木斯可以加速復原 (雖然在已經出現AMS症狀的人, 服用丹木斯的研究報告目前不多)
在偏遠地區, 如果經過休息或治療, 仍持續有AMS症狀應該下降 500-1000 公尺. 如果無法下降, 可以採取下列方式: 給予類固醇 DEXAMETHASONE 4-8 mg 每六小時吃一次, 給予氧氣, 使用加壓艙.
The treatment of mild-to-moderate acute mountain sickness (Table 4) generally consists of a day of rest, NSAIDs for headache, and possibly antiemetic drugs. One small, placebo-controlled, crossover trial showed that ibuprofen reduced headache significantly in affected persons. Treatment with oxygen and acetazolamide may also facilitate more rapid recovery, although there are only limited data from randomized trials to support the benefit of acetazolamide in persons in whom acute mountain sickness has already developed. In remote areas, a descent of 500 to 1000 m is indicated if symptoms of acute mountain sickness persist despite a day of rest and symptomatic treatment. If descent is not possible because of logistical constraints or the person’s condition, improvement sufficient to allow descent can be achieved with one or a combination of the following interventions: administration of dexamethasone at a dose of 4 to 8 mg every 6 hours, provision of supplemental oxygen (2 to 4 liters per minute), or treatment in a manually pressurized, body-length, portable hyperbaric bag.

嚴重症狀需要立即下降, 因為可能已經出現高海拔腦水腫, 或高海拔肺水腫
高海拔肺水腫病患, 可以使用氧氣降低肺動脈壓, 下降至較低海拔, 使用肺動脈擴張劑(NIFEDIPINE). 有文獻報告指出犀利士或威而鋼治療高海拔肺水腫會有好處, 但類固醇 地塞米松 dexamethasone 則無證據支持。
雖然治療高海拔肺水腫主要是需要下降, 但將一個輕度至中度症狀的清醒病患, 留置在偏遠地區, 使用氧氣及口服肺血管擴張劑, 同時在當地有急救設施或有醫師可以幫助觀察, 是合理的,.
利尿劑對於高海拔肺水腫無效.
Immediate descent is lifesaving when severe symptoms suggest the onset of high-altitude cerebral edema or high-altitude pulmonary edema. In persons with high-altitude pulmonary edema, pulmonary-artery pressure should be lowered by means of supplemental oxygen (2 to 4 liters per minute), descent to a lower altitude, or pulmonary vasodilators (of which only nifedipine has been tested in a prospective study, which was uncontrolled). Anecdotal reports describe a benefit of phosphodiesterase-5 inhibitors for the treatment of high-altitude pulmonary edema, but they do not provide support for the use of dexamethasone. Although descent to a lower altitude is the primary goal for the management of high-altitude pulmonary edema in remote areas, allowing a fully conscious person with mild-to-moderate high-altitude pulmonary edema to remain in a mountainous resort area is reasonable when supplemental oxygen and oral pulmonary vasodilators can be provided under the supervision of a local physician or in an emergency facility. There is no role for diuretics in the treatment of high-altitude pulmonary edema.

野外與登山醫學---202207212001高海拔肺水腫 HAPE 發作時間

2023-10-08 22:40
HAPE典型發作在到達高海拔的第2-5天, 在這裡將幾篇看過的文獻資料都放上來. 大家引用的應該都是相同資料. 

(筆記: High Altitude Pulmonary Edema (HAPE))
2013 Acute High-Altitude Illnesses (NEJM )
通常發生在海拔 3000 公尺以上, 兩天後 在海拔 2500-3000 公尺以下較罕發生
High-Altitude Pulmonary Edema High-altitude pulmonary edema is characterized by loss of stamina, dyspnea, and dry cough with exertion, followed by dyspnea at rest, rales, cyanosis, cough, and pink, frothy sputum.13 Deterioration in gas exchange also increases the risk of high-altitude cerebral edema. This condition develops 2 or more days after exposure to altitudes above 3000 m and is rare in persons at altitudes below 2500 to 3000 m. The risk increases with increased altitude and faster ascent. For example, the incidence among persons with an unknown history of high-altitude pulmonary edema is 0.2% if they ascend to 4500 m in 4 days and 2% if they ascend to 5500 m in 7 days; the incidence increases to 6% and 15%, respectively, when these altitudes are reached within 1 to 2 days. The risk is further increased among persons with a history of high-altitude pulmonary edema (e.g., the risk of recurrence is 60% among persons who ascend to 4500 m in 2 days).14 The estimated mortality among persons with untreated highaltitude pulmonary edema is 50%. This disorder is a noncardiogenic pulmonary edema caused by exaggerated hypoxic pulmonary vasoconstriction and abnormally high pulmonary-artery pressure and capillary pressure.15 These high pressures lead to a noninflammatory and hemorrhagic alveolar capillary leak that secondarily may evoke an inflammatory response.16

2. 2022年 StatPerls: High Altitude Pulmonary Edema- Jacob D. Jensen; Andrew L. Vincent.
Author Information
Authors Jacob D. Jensen1; Andrew L. Vincent2.
Affiliations
1 OSF St Francis Med Center EM Residency
2 University of Illinois-Peoria 美國皮奥里亚(伊利诺伊州)大學
Last Update: May 1, 2022. 

History and Physical
HAPE typically occurs 2 to 5 days after arrival at altitude. It has an insidious onset with a non-productive cough, decreased exercise tolerance, chest pain, and exertional dyspnea. Without treatment, it can progress to dyspnea at rest and severe exertional dyspnea. A cough may become productive of pink and frothy sputum or frank blood. The patient also may have rales or wheezes, central cyanosis, tachypnea, and/or tachycardia. SpO2 is often 10% less than expected for altitude, and the patient often will appear better than expected given their level of hypoxemia and SpO2 value, which typically resides around 40% to 70%.


下面這篇是印度的研究, 發表於 2012年 五月.
Indian J Occup Environ Med. 2012 May-Aug; 16(2): 59–62. doi: 10.4103/0019-5278.107066 PMCID: PMC3617508 PMID: 23580834
High altitude pulmonary edema-clinical features, pathophysiology, prevention and treatment
Swapnil J. Paralikar
CLINICAL FEATURES
HAPE presents within 2-5 days of arrival at high altitude. It is rarely observed below altitudes of 2500-3000 m and after 1 week of acclimatsation at a particular altitude.

野外與登山醫學---202203191929氣管擴張劑降低高海拔肺水腫機率從77%降低至33%

 

原文

We found that prophylactic inhalation of salmeterol decreased the incidence of high-altitude pulmonary edema in susceptible subjects by more than 50 percent, from 74 percent with placebo to 33 percent. Several mechanisms could have contributed to this favorable effect.2002年5月23日

Abstract

BACKGROUND

Pulmonary edema results from a persistent imbalance between forces that drive water into the air space and the physiologic mechanisms that remove it. Among the latter, the absorption of liquid driven by active alveolar transepithelial sodium transport has an important role; a defect of this mechanism may predispose patients to pulmonary edema. Beta-adrenergic agonists up-regulate the clearance of alveolar fluid and attenuate pulmonary edema in animal models.

METHODS

In a double-blind, randomized, placebo-controlled study, we assessed the effects of prophylactic inhalation of the beta-adrenergic agonist salmeterol on the incidence of pulmonary edema during exposure to high altitudes (4559 m, reached in less than 22 hours) in 37 subjects who were susceptible to high-altitude pulmonary edema. We also measured the nasal transepithelial potential difference, a marker of the transepithelial sodium and water transport in the distal airways, in 33 mountaineers who were prone to high-altitude pulmonary edema and 33 mountaineers who were resistant to this condition.

RESULTS

Prophylactic inhalation of salmeterol decreased the incidence of high-altitude pulmonary edema in susceptible subjects by more than 50 percent, from 74 percent with placebo to 33 percent (P=0.02). The nasal potential-difference value under low-altitude conditions was more than 30 percent lower in the subjects who were susceptible to high-altitude pulmonary edema than in those who were not susceptible (P<0.001).

CONCLUSIONS

Prophylactic inhalation of a beta-adrenergic agonist reduces the risk of high-altitude pulmonary edema. Sodium-dependent absorption of liquid from the airways may be defective in patients who are susceptible to high-altitude pulmonary edema. These findings support the concept that sodium-driven clearance of alveolar fluid may have a pathogenic role in pulmonary edema in humans and therefore represent an appropriate target for therapy.

野外與登山醫學-預防高海拔疾病藥物使用方式與時間

高海拔疾病主要有三種 1. AMS 急性高山病, 2.HACE 高海拔腦水腫, 3. HAPE 高海拔肺水腫
預防高海拔疾病 high altitude illness (包括 AMS acute mountainsickness, 高海拔腦水腫 HAPE high altitude cerebral edema, 高海拔肺水腫 HAPE high altitude pulmonary edema)
主要的藥物有三種. 丹木斯 acetazolamide. 鈣離子阻斷劑 nifedipine. 類固醇 地塞米松 deXamethasone. 其他輔助藥物可以攜帶止吐藥物. 止痛藥物.
至於威而鋼/犀利士, 並沒有預防AMS或HACE的效果. 僅能預防HAPE. 但如果過去沒有罹患過 HAPE 並不需要預防性使用. 而用以治療 HAPE 的藥物選單並不包含威而鋼/犀利士, 目前研究樣本仍不足, 且威而鋼價格昂貴, 預防 HAPE 效果並不比 nifedipine 佳,. 因此不建議特別購買. 如果身邊剛好有帶.在罹患 HAPE 或許可考慮服用.
(如果容易出現AMS的人, 也可考慮預防性吃止痛藥, ibuprofen or acetaminophen.)
提醒大家一點. 飛機的機艙壓力相當於海拔 2500 公尺氣壓. 因此, 旅遊行程第一天如果海拔已經超過 2500 公尺,. 從搭飛機當天就要當成 day 1. 往回推 24 小時開始預防性服用藥物.

針對高海拔疾病, 主要預防方式是
a. 緩慢上升: 海拔 2500 公尺以上, 每天上升不要超過 500 公尺.
b. 高度適應: 在上升到高海拔 2500 公尺之前, 先去高海拔地區, 進行高度適應
如果無法做到以上兩者, 考慮藥物預防的方式. 建議如下.
1. 預防AMS和 HACE
丹木斯是預防 AMS. HACE, 台灣賣的丹木斯主要是 250mg 的. 預防性使用, 先找出行程之中海拔會超過 2500 公尺的時間點. 往回推 24 小時, 開始服藥. 如果過去不曾吃過, 建議在平地先試吃, 因為丹木斯會有一些副作用, 包括舌頭的異常味覺, 手指腳趾的麻木感覺. 在平地先使用是要了解藥物在自己身體會出現哪些副作用. 如果無法忍受, 可能不適合在山上服用, 如果有過敏, 可就近找醫療院所看診. 丹木斯每次吃 125 mg. 常見劑量是半顆. 一天兩次(每 8 到 12 小時)服用一次. 如果行程的危險分級屬於低度危險. 不太需要使用. 如果行程屬於中度或高度危險. 則考慮藥物預防. 在穩定的海拔, 例如 3500 公尺上下. 如果預計未來海拔都差不多, 每天營地(睡眠海拔)高度落差不會超過 500 公尺. 在穩定海拔連續服用 2 天之後如果沒有高海拔症狀, 可考慮停藥. (NEJM 2013 guideline 裡面是寫 2-3 天. 如果是快速上升至極高海拔 WMS 2014 和 2019 兩篇 guideline 說可以吃滿 2-4天), 或者到達最高海拔, 行程要開始下降即可停用.
類固醇deXamethasone, 在海拔到達 2500 公尺可以開始服用, 連續服用不要超過十天, 類固醇停用之後可能會突然發生高海拔疾病症狀, 要小心, 類固醇劑量可以每次吃 4mg. 每 12 小時吃一次, 類固醇deXamethasone在服用之後要數小時才會開始產生作用.
uptodate 建議預防性使用不要連續超過七天. 2014 WMS 指引建議預防性使用不要連續超過 10 天.

 
2. 預防 HAPE
Nifedipine: 在 2013 NEJM 指引放在預防HAPE第一線用藥.
只有先前曾罹患HAPE的人才需要使用藥物預防HAPE，預防 HAPE 除了不要爬升太快, nifedipine 是首選藥物，在上升前一天就要開始使用，跟丹木斯相同, 先找出海拔開始超過 2500 公尺的時間點, 往回推前 24 小時開始吃藥. 服藥持續到高度下降，或在穩定海拔超過四天。如果上升速率超過建議速率，則延長服藥時間, 在目標海拔持續使用藥物七天. 使用 nifedipine 每天總量是 60 mg. 依照買到的不同劑型分次服用. 如果是 30mg 長效錠, 每天吃兩次(間隔 8-12 小時), 如果是 20 mg 長效錠, 每天吃三次(間隔 6-8 小時).
威而鋼/犀利士: 效果並沒有優於 nifedipine. 但價格卻貴非常多, 在 NEJM 2013 指引, 放在預防HAPE第二線用藥

 
丹木斯預防 HAPE 學理上有效. 但缺乏研究證據支持. (因丹木斯可加速高度適應).
類固醇在 2013 年NEJM 高海拔疾病文獻, 可用於預防HAPE. 但 2014 WMS 文獻則認為目前研究不夠多.

 
2014 WMS文獻認為, 關於犀利士和類固醇預防 HAPE 的建議仍需更多研究
心臟衰竭造成的肺水腫使用氣管擴張劑通常無效. 氣管擴張劑臨床上用於治療氣喘\肺氣腫急性發作病患, 但 salmeterol 卻可以用在輔助預防 HAPE. 不過因臨床研究很少, 僅建議輔助 nifedipine 使用.
參考資料
1. 2014 WMS 
Acetazolamide carries a low risk of cross-reactivity in persons with sulfonamide allergy, but persons with known allergy to sulfonamide medications should consider a supervised trial of acetazolamide before the trip, particularly if planning travel into an area remote from medical resources.33 A history of anaphylaxis to sulfonamide medications should be considered a contraindication to acetazolamide. Acetazolamide and dexamethasone should be started the day before ascent (but will still have beneficial effects if started on the day of ascent). For individuals ascending to and staying at the same elevation for more than several days, prophylaxis may be stopped after 2 days at the target altitude. Individuals ascending faster than the recommended ascent rates should continue prophylaxis for a total of 4 days after arrival at the target altitude. Recommendation Grade: 2C. For individuals ascending to a high point and then descending toward the trailhead (eg, descending from the summit of Kilimanjaro), prophylactic medications should be stopped once descent is initiated.
2. 另外,. 使用 丹木斯 預防 AMS. NNT=8 http://www.thennt.com/nnt/acetazolamide-prevention-acute-mountain-sickness-ams/
BENEFIT IN NNT= 1 in 8 patients had prevention of AMS at high altitude 24 hours after arrival
3. 2013 NEJM acute high altitude illness
4. 無法預防高海拔疾病的藥物
5. 2002年的研究 salmeterol 預防 HAPE https://www.ncbi.nlm.nih.gov/pubmed/12023995
N Engl J Med. 2002 May 23;346(21):1631-6. Salmeterol for the prevention of high-altitude pulmonary edema.
Sartori C1, Allemann Y, Duplain H, Lepori M, Egli M, Lipp E, Hutter D, Turini P, Hugli O, Cook S, Nicod P, Scherrer U.
BACKGROUND:
Pulmonary edema results from a persistent imbalance between forces that drive water into the air space and the physiologic mechanisms that remove it. Among the latter, the absorption of liquid driven by active alveolar transepithelial sodium transport has an important role; a defect of this mechanism may predispose patients to pulmonary edema. Beta-adrenergic agonists up-regulate the clearance of alveolar fluid and attenuate pulmonary edema in animal models.
METHODS:
In a double-blind, randomized, placebo-controlled study, we assessed the effects of prophylactic inhalation of the beta-adrenergic agonist salmeterol on the incidence of pulmonary edema during exposure to high altitudes (4559 m, reached in less than 22 hours) in 37 subjects who were susceptible to high-altitude pulmonary edema. We also measured the nasal transepithelial potential difference, a marker of the transepithelial sodium and water transport in the distal airways, in 33 mountaineers who were prone to high-altitude pulmonary edema and 33 mountaineers who were resistant to this condition.
RESULTS: 安慰劑預防 HAPE 效果 33%, salmeterol 預防 HAPE 效果 74%
Prophylactic inhalation of salmeterol decreased the incidence of high-altitude pulmonary edema in susceptible subjects by more than 50 percent, from 74 percent with placebo to 33 percent (P=0.02). The nasal potential-difference value under low-altitude conditions was more than 30 percent lower in the subjects who were susceptible to high-altitude pulmonary edema than in those who were not susceptible (P<0.001).
CONCLUSIONS:
Prophylactic inhalation of a beta-adrenergic agonist reduces the risk of high-altitude pulmonary edema. Sodium-dependent absorption of liquid from the airways may be defective in patients who are susceptible to high-altitude pulmonary edema. These findings support the concept that sodium-driven clearance of alveolar fluid may have a pathogenic role in pulmonary edema in humans and therefore represent an appropriate target for therapy.

野外與登山醫學 --- 202112181034High-altitude pulmonary edema in children 小兒AMS及高海拔肺水腫案例報告

REPORTS OF INCIDENCE OF AMS AND HAPE IN CHILDREN

Children at High Altitude: An International Consensus Statement by an Ad Hoc Committee of the International Society for Mountain Medicine, March 12, 2001
關於小兒高海拔肺水腫案例很少. 這篇研究是 2001年發表的
下面開始用google自動翻譯.

簡介
每年都有成千上萬的低地兒童平安無事地前往高海拔地區。大多數這些兒科攀登涉及到山區度假勝地的旅行，尤其是在北美和歐洲，還有一小部分涉及到非工業化國家的偏遠高地地區的旅行。此外，越來越多的兒童因父母的職業而搬到高海拔地區與家人一起居住。儘管對大多數人來說，高海拔旅行不會發生意外，但其中一些兒童會出現可能歸因於高海拔暴露，但醫學或科學文獻中幾乎沒有記錄。在這裡，我們概述了可用的案例。本共識聲明涉及兒科人群中嚴重高原病的發生、預防、識別和治療。不幸的是，兒童暴露在高海拔地區的特殊風險很少被研究，許多建議必須從成人數據中推斷出來，並適當考慮生長和發育的影響（Berghold，2000）。
本聲明的目的是為臨床醫生提供有關兒科人群高原旅行建議的信息。通過更好的教育，父母可以就旅行做出明智的決定
如果發生高原反應，他們的孩子可以被賦予檢測高原反應的能力。
上面這張圖照片，將HAPE的部分動畫下來，由數據可以看到，正在發生的HAPE的兒童案例監護人，有一個例子是西藏的
美國報告的報告數量比較多​​，我猜這兩者之間可能不是機率兩地的醫療與學術風氣不同的

西藏有很多沒被的案例記錄1.1.1。兒童 AMS 的發病率似乎與在成人中觀察到的相同（見表 1；以及 Theis 等，1993；Wu，1994；Yaron 等，1998；Yaron 等，2000）。 1.1.2. 低海拔地區兒童到高海拔地區旅行和高海拔地區兒童從海平面附近旅行返回的 HAPE 的性質和發病率可能不同。與成人相比，低地兒童患 HAPE 的風險可能沒有增加。居住在高海拔地區的兒童比成人更容易患上折返性 HAPE（Marticorena 等，1964；Menon，1965；Scoggin 等，1977；Hultgren 和 Marticorena，1978；Fasules 等，1985）；這些研究涉及高海拔居民重新上升到高海拔，而不是低海拔居民前往高海拔。青藏高原旅行兒童的 HAPE 發生率也與同一組的成人相似（見表 1；Wu，1994）。然而，並發病毒感染可能易患 HAPE（Durmowicz 等，1997），並且這種感染在幼兒中在統計學上更為常見。共識委員會成員報告了兒童 HAPE 個別病例的經驗。
1.1.3. 沒有關於兒童 HACE 發病率的公開信息，文獻中也沒有病例報告。
1.2 兒童急性高原病的危險因素。很少有信息可以概述特別是兒童高原病的風險因素。表 3 包含從一些兒科和一些成人研究中推斷出的高原病的可能風險因素。1.3 急性高原病的症狀和體徵
在兒童中。在所有年齡段（兒童和成人），高原病的症狀都是非特異性的，可能與不相關的變量混淆，例如並發疾病、飲食不當、中毒或與遠程旅行相關的心理因素（Berghold 和 Schaffert，1999）。然而，當與孩子一起上升時，除了考慮針對其他可能的原因進行治療外，明智的做法是假設此類症狀與海拔高度相關並採取適當的措施。
1. 在年齡較大的兒童（0.8 歲）中，假設高原病的表現方式與成人大致相同。
2. 3 歲以下，到任何新環境旅行可能會導致睡眠、食慾、活動和情緒的改變。將單獨旅行引起的行為變化與高原疾病引起的變化區分開來可能很困難。由於
幼兒感知和表達的發展水平存在差異，即使他們會說話，他們也不是高原病症狀的可靠報告者。
症狀可能表現為非特異性行為改變，而不是頭痛或噁心的具體主訴。幼兒急性高山病的典型症狀包括煩躁不安、食慾下降和可能嘔吐、玩耍減少和睡眠困難。這些症狀通常在上升到海拔 4 到 12 小時後開始. 路易斯湖評分的改進版已經
開發出來，用於評估非常年幼兒童的非特異性症狀，並且可能對評估未說話的兒童有用；參見附錄 B（Yaron 等，1998）。然而，目前該評分還沒有被父母或醫生在高海拔兒童管理決策中常規使用進行評估。該分數已被驗證為
父母使用時具有較高的觀察者間一致性，並且它可能有助於對父母進行 AMS 症狀的教育（Yaron 等，2000）。
3. 一些年齡較大的兒童，特別是3-8歲的兒童，以及學習或交流有困難的兒童，也可能對症狀描述不力，導致高原病難以識別。
1.4 預防兒童急性高原病。沒有關於預防兒童高原病的研究；然而，我們假設成人的預防原則也適用於兒童。
1.4.1. 分級上升。緩慢的分級上升，留出適應環境的時間，是有幫助的。已推薦2500米以上每天300米的新生速度和每1000米休息日，但尚不清楚是否更適合兒童或多或少謹慎的建議。與成人相比，關於兒童對海拔的適應情況的數據很少。在一份記錄了兒童心率和動脈血氧飽和度變化的報告中發現，兒童的適應能力至少與成人一樣好，甚至比成人好。
7 至 9 歲的兒童及其成年父母在緩慢的梯度上升過程中（Tuggy 等，2000）。
1.4.2. 通常應避免使用藥物預防來幫助兒童適應環境，因為在大多數情況下緩慢上升可達到相同的效果，並最大限度地減少兒童不必要的藥物使用。在極少數情況下，當快速上升不可避免時，可能需要使用乙酰唑胺幫助兒童適應環境。已知先前對 AMS 易感的兒童可能會受益於預防以幫助適應環境。乙酰唑胺確實會出現副作用，例如感覺異常、皮疹和可能的脫水；因此不應鼓勵使用。磺胺過敏是使用乙酰唑胺的禁忌症。
1.4.3. 教育。兒童及其照顧者應在高原旅行（2500 米以上）之前熟悉高原病的症狀及其管理。父母還應該了解他們的孩子在旅行期間的反應，無論海拔如何，以便能夠將高海拔疾病與簡單的
旅行症狀區分開來。
1.4.4. 應急預案。前往偏遠海拔地區的所有團體在出行前應制定應急預案，以確保必要時疏散該黨的患病成員。應急計劃的一部分應包括提供通信以促進疏散。如果孩子正在前往高海拔地區，應該可以立即（數小時內）下降或獲得氧氣。當下降需要數天或需要在下降前進一步上升時，應避免在海拔高度逗留。
1.4.5. 團體旅遊。學校探險是年齡較大的兒童的一種流行教育體驗。計劃學校團體遠征到（睡眠）海拔 2500 米以上的組織必須規劃一個允許分級上升、休息日、輕鬆下降以及在生病時靈活的行程的組織。遠征前 p5。醫療和疏散保險（適用於所有旅行者）。
1.5 兒童急性高原病的治療。沒有關於治療兒童急性高原病的研究。然而，遵循表 4 中概述的適當兒科藥物劑量的成人治療流程似乎是合適的。 在管理患有急性高山病的兒童時要更加謹慎，並且在症狀出現後更早下降可能比實際情況更謹慎對於成年人來說，因為兒童期 AMS 的自然病程沒有得到很好的表徵。在可能的情況下，下降時應盡量少用力，這可能會加劇症狀，並且在下降過程中應在可行的情況下抱起孩子。
2.有症狀的高原肺動脈高壓
有症狀的高原肺動脈高壓 (SHAPH) 包括肺動脈高壓的急性加重以及亞急性嬰兒高山病 (SIMS) 或高原心髒病綜合徵。
在與並發病毒感染相關的生活或旅行到高海拔地區的嬰兒中觀察到肺動脈壓力急劇增加（Susan Niermeyer，未發表的觀察結果）。治療的重點是給氧和下降。SHAPH 的亞急性形式幾乎只發生在持續暴露於 3000 m 以上海拔 1 個月以上的低海拔嬰兒（1 歲以下）（Wu 和 Liu，1955；Khoury 和 Hawes，1963；Sui 等人） ., 1988; Wu, 1994)。SHAPH 的風險可能存在種族差異。中國嬰兒的發病率為 1%
3050 到 5188 m (Wu, 1994)。在這種情況下，嬰兒會出現缺氧性肺動脈高壓和隨之而來的右心室心力衰竭。表現始於進食不良、嗜睡和出汗。之後，呼吸困難、紫紺、咳嗽、煩躁、失眠、肝腫大、水腫、少尿等心力衰竭的跡象可能會變得明顯。管理不同於急性高山病的管理應包括以下內容：
1. 評估每個孩子的既往病史。
2. 對父母、工作人員和孩子進行關於高原疾病和其他探險健康危害的教育。
3. 對工作人員進行野外急救培訓並準備合適的急救箱。
4. 應急和疏散計劃，包括緊急情況下的通訊方式。
5. 醫療和疏散保險（適用
於所有旅行者）。
1.5 兒童急性高原病的治療。
沒有關於治療兒童急性高原病的研究。然而，遵循表 4 中概述的
適當兒科藥物劑量的成人治療流程似乎是合適的。在管理患有急性高山病的兒童時要更加謹慎，並且在症狀出現後更早下降可能比實際情況更謹慎對於成年人來說，因為兒童期 AMS 的自然病程沒有得到很好的表徵。在可能的情況下，下降應該涉及最小的勞累，這可能會加劇症狀，並且在下降過程中，應在可行的情況下攜帶兒童。
2. 症狀性高原肺動脈高壓
症狀性高原肺動脈高壓（SHAPH）包括肺動脈高壓急性加重以及亞急性嬰兒高山病（SIMS）或高原心髒病綜合徵。在與並發病毒感染相關的生活或旅行到高海拔地區的嬰兒中觀察到肺動脈壓力急劇增加（Susan Niermeyer，未發表的觀察結果）。
治療的重點是給氧和下降。

SHAPH 的亞急性形式幾乎只發生在低海拔血統的嬰兒（1 歲以下）中暴露在海拔超過 3000 米的地方超過1 個月（Wu 和 Liu，1955；Khoury 和Hawes，1963；Sui 等，1988；Wu，1994）。有可能在SHAPH的危險種族差異。
在3050 至 5188 米的中國嬰兒中，發病率為 1% （Wu，1994）。在這種情況下，嬰兒會出現缺氧性肺動脈高壓和隨之而來的右心室心力衰竭。表現始於進食不良、嗜睡和出汗。之後，呼吸困難、紫紺、咳嗽、煩躁、失眠、肝腫大、水腫、少尿等心力衰竭的跡象可能會變得明顯。管理不同於急性高山病，其目的是控制充血性心力衰竭和逆轉肺動脈高壓。

治療包括吸氧、藥物利尿和緊急下降。

3. 嬰兒猝死綜合徵 (SIDS)由於存在相互矛盾的報告，目前尚不清楚暴露於高海拔是否會增加 SIDS 的風險（Barkin 等，1981；Getts 和 Hill，1982；Kohlendorfer 等，1998）。俯臥位是海拔和海平面的重要輔助因素（Kohlendorfer 等，1998）。與在海平面上一樣，嬰兒總是仰臥睡覺並避免被動接觸煙草煙霧可以降低 SIDS的風險（Wisborg 等，2000）。關聯的可能性需要仔細考慮與年幼（1 歲）嬰兒一起上升到海拔高度。還有一個理論上的風險和一些證據表明暴露於高海拔地區可能會干擾出生後的正常呼吸適應（Niermeyer，1997 年；Parkins 等，1998 年）。

4. 寒冷暴露
嬰兒和幼兒由於表面積與體積之比很大，因此特別容易受到寒冷的影響。在遠足期間必須被抱起的孩子不會通過肌肉活動產生熱量，並且有體溫過低的風險。足夠的衣服對於防止痛苦、體溫過低和凍傷至關重要。委員會了解到一些四肢凍傷的案例，包括那些需要截肢的案例（未發表的意見，S. Kriemler；未發表的意見，JA Litch）。

5. 陽光照射
高海拔地區雪和較薄的大氣層的反射使太陽紫外線輻射灼傷的風險比海平面高。如果暴露在過多的陽光下，兒童比成人更容易被灼傷。需要適當的防曬霜（UVA 和 B，SPF 30 美元，在日曬前塗抹）、帽子和長袖以及護目鏡，以防止曬傷或雪盲。

6. 帶孩子在高海拔環境中旅行時需要考慮的其他因素 帶孩子旅行對父母和孩子來說都是非常有益的。對於很多帶著孩子上學的家長來說山上，這次旅行是一個遠離日常活動的放鬆機會。但是，應考慮許多因素，這些因素可能會改善兒童和父母對此類旅行的享受（Berghold 和 Moravec，1994 年）。

1.無聊。幼兒的注意力通常很短，並且在相對較短的距離旅行後很容易感到無聊。應謹慎選擇刺激性的行程。
2.身體能力。已經估計了幼兒（在海平面）可能行走的距離（Gentile 和 Kennedy，1991），但這些估計只能用作可以針對每個兒童進行調整的指導方針。應該強調的是，孩子們應該只走他們想要走的路。
3. 食物。一些年幼的孩子可能對環境變化的適應能力很差，拒絕不熟悉的食物。在可能的情況下，在高海拔旅行之前嘗試食物是有幫助的。確保充足的食物和液體攝入很重要。
4. 衛生。在偏遠的徒步旅行中，對於試圖為孩子保持適當衛生的父母來說，帶著年幼的嬰兒旅行可能會特別緊張。
5. 並發疾病。腸胃炎在兒童旅行者中可能並不比在成人中更常見。兒童更容易出現嚴重的、危及生命的胃腸炎脫水，因此每個醫療包都應包含製作安全口服補液溶液的用品。
7. 已有疾病的兒童患有某些潛在慢性疾病的兒童患慢性病惡化或與海拔直接相關的疾病（如 HAPE）的風險可能會增加。幾乎沒有數據可用於確定特定疾病的風險，例如囊性纖維化或早產兒慢性肺病（支氣管肺發育不良）。然而，通過首先了解與高原有關的疾病發展的已知風險因素，然後評估每個孩子的狀況如何在缺氧環境中影響他或她的心肺生理，就有可能確定發展為高原相關疾病的相對風險。高海拔並發症。例如，兩者都相對缺乏增加分鐘高原通氣和肺血管過度灌注，例如在沒有肺動脈的個體中看到的，是發生 HAPE 的危險因素（Matsuzawa 等，1989；Selland 等，1993；Sebbane 等，1997） . 因此，合乎邏輯地認為，先天性心臟缺陷導致肺血管床過度灌注的兒童，例如心房和室間隔缺損、單側肺動脈缺如和動脈導管未閉，會增加發展的風險。與高原有關的疾病，如 HAPE。同樣，患有繼發於早產或囊性纖維化的嚴重肺部疾病且海平面 PaCO2 水平升高的兒童在受到海拔高度壓力時可能無法增加他們的每分鐘通氣量，因此有在海拔高度生病的風險。患有唐氏綜合症的兒童發生阻塞性呼吸暫停和換氣不足以及導致肺血流量增加的先天性心臟缺陷的發生率很高。

患有非心肺疾病的兒童在高海拔地區患病的風險也可能增加，這取決於疾病對高海拔壓力的反應。例如，一名繼發於腎上腺生殖器綜合徵的皮質醇缺乏症兒童在中等海拔地區發展為 HAPE，兩名最近完成化療的癌症兒童也是如此（未發表的觀察，AG Durmowicz）。不再接受藥物治療的兒童可能會在低至 2700 m 的地方出現新發或複發性癲癇發作（未發表的觀察，PH Hackett）。此外，患有鐮狀細胞性貧血的兒童在高海拔地區發生鐮狀細胞危象的風險似乎更高（Mahony 和 Githens，1979 年）。
最重要的是，如果父母決定帶著患有慢性疾病的孩子到高海拔地區旅行，則必須制定特殊計劃以確保充足的物資和緊急疏散。這可能意味著限制前往更發達的海拔目的地的旅行，而不是孤立的偏遠地區旅行。

8. 關於帶孩子爬山的特殊注意事項的聲明
1 沒有關於孩子爬山的絕對安全高度的數據。
2. 海拔2500米以上，尤其是2500米以上的睡眠，有患急性高原病的風險。
3. 並發疾病可能會增加患高原病的風險。
4. 長期（數週）暴露於高原缺氧對整體生長以及大腦和心肺發育的影響尚不清楚。


8.1 旅行地點。前往工業化國家的山區和滑雪勝地的高海拔地區可以輕鬆快速地獲得醫療服務，應與在偏遠山區和無法獲得高水平醫療技術的地區進行遠程旅行不同。
1. 工業化國家的山地旅遊景點和滑雪場大多位於3000米以下，大部分遊客會在3000米以下睡覺。
在這個海拔高度，急性高山病很常見，嚴重高山病的風險可能很小。一旦被識別，在大多數情況下，可以通過氧氣和/或下降來有效控制高原病。在旅遊活動（乘坐纜車、山路旅行和滑雪旅行）期間上升到海拔高度高於度假村位置，大約 4000 m，通常很短（小時）並且可能帶來最小的額外風險。步行或騎馬在 3000 米以上的長途旅行應緩慢分級和謹慎上升，以減少高原病的可能性。
2. 在無法快速獲得醫療服務的偏遠山區進行攀登時應更加謹慎。睡眠海拔等於或低於 3000 米的攀登，患嚴重高原病的風險較低；但是當發生 HAPE 或 HACE 時，管理可能比發達地區更困難。在這種情況下，較高的攀登應採用緩慢分級的攀登、休息（適應）日和仔細的應急計劃。

8.2 孩子的年齡

1. 高原病在無法報告典型的高山病症狀的兒童（3 歲）中尤其難以識別。同樣，一些 3 至 8 歲的兒童可能擅長報告症狀，但對於這個年齡段的年幼兒童和學習困難的兒童，他們在表達急性高原病症狀的經歷方面表現不佳，則需要格外小心。年齡較大的兒童（0.8 歲）通常已達到報告這些症狀所需的發育水平。
2. 很多沒有語言的孩子到北美山脈3000米的度假村旅行沒有並發症，但更高的攀登和偏遠地區的攀登需要格外小心。
3. 對於出生後最初幾周和幾個月的嬰兒，可能存在一些額外的理論擔憂，即暴露於 2500m 以上超過幾個小時可能會影響正常的呼吸模式（Parkins 等，1998）。


8.3 海拔高度暴露的長度
1. 3000 m 以上的長時間（0.1 天）或需要在 3000 m 以上的睡眠會增加急性高山病的風險，應謹慎進行緩慢梯度上升、內置休息日和應急計劃.
2. 如果孩子因父母的職業而在海拔 2500 米以上旅行並且預計將在高海拔地區長期居住，則應按照第 1.4 節所述進行緩慢的分級上升。對於計劃永久居住在高海拔地區的嬰兒（1 歲），由於 3000 m 以上的 SIMS 風險很小，一些權威機構建議將上升到高海拔地區推遲到一歲以後。如果要避免父母分離，這通常是不切實際的。因此，在爬升前仔細體格檢查和初步適應高海拔後，應密切跟踪嬰兒的生長百分位；脈搏血氧飽和度可能有用，尤其是在睡眠期間，應定期監測心電圖以了解右心室肥厚的發展。


9. 結論
如果準備充分，帶孩子的野外旅行對父母和照顧者來說是一種有益的體驗。上升到海拔為這種荒野旅行增加了額外的維度，必須仔細考慮。不幸的是，直接指導的數據很少，但考慮到一些兒科研究和成人數據的推斷，為安全實踐提供了一個框架。這裡描述的共識觀點提供了保守的建議，應該對需要帶孩子爬高海拔的醫生有幫助。

INTRODUCTION
EACH YEAR MANY THOUSANDS of lowland children travel to high altitude uneventfully. The majority of these pediatric ascents involve trips to mountain resorts, especially in North America and Europe, and a smaller proportion involve journeys to remote highland areas in nonindustrialized nations. In addition, an increasing number of children are moving to reside with their families at high altitude as a result of parental occupation. Although altitude travel is without incident for most, some of these children develop symptoms that may be
attributed to altitude exposure, but there has been little documentation in the medical or scientific literature. Here we outline cases where available. This consensus statement is concerned with the incidence, prevention, recognition, and treatment of serious altitude illness in the pediatric population. Unfortunately, the particular risks of exposure of children to high altitude have been little studied and much of the advice
must necessarily be extrapolated from adult data with due consideration of the influence of growth and development (Berghold, 2000). 
The aim of this statement is to offer information for clinicians providing advice concerning altitude travel in the pediatric population. Through better education, parents can make informed decisions regarding travel  ith
their children and can be empowered to detect altitude illness, should it occur.
1994年, 看名字應該是大陸的研究, 西藏海拔 4550, 收入 465位小孩及 5335 位成人, AMS機率 34%, 跟大人 38.2% 差不多, 小兒 HAPE 1.5%, 跟大人 1.27% 也差不多.
科羅拉多的數據, 海拔 2835公尺, 3488 公尺, 3109公尺, 海拔比西藏低很多, 所以成人與小兒都沒有罹患HAPE的案例

上面這張圖太大, 將HAPE的部分裁剪下來, 由數據可以看到, 發生HAPE的兒童案例不多, 有一例是西藏的報告
美國的報告數量比較多, 我猜這之間差異可能不是發生機率, 而是兩地的醫療水準與學術風氣不同

1.1.1. The incidence of AMS in children seems to be the same as that observed in adults (see Table 1; and Theis et al., 1993; Wu, 1994; Yaron et al., 1998; Yaron et al., 2000). 
1.1.2. The nature and incidence of HAPE may differ between children resident at low altitude who travel to high altitude and those resident at high altitude who return from travels near sea level. Lowland children probably have no increased risk of HAPE compared to adults.
Children resident at high altitude are more likely than adults to develop reentry HAPE (Marticorena et al., 1964; Menon, 1965; Scoggin et al., 1977; Hultgren and Marticorena, 1978; Fasules et al., 1985); these studies involved high altitude residents reascending to altitude, rather than low altitude residents journeying to high altitude. The incidence of HAPE in children traveling on the Tibetan plateau was also found similar to adults among the same group (see Table 1; and Wu, 1994). However, intercurrent viral infections may predispose to HAPE (Durmowicz et al., 1997), and such infections are statistically more frequent among young children. Members of the consensus committee report experience of individual cases of HAPE in children.
1.1.3. There is no published information about the incidence of HACE in children and no case reports in the literature. 
1.2 Risk factors for acute altitude illness in children. Very little information is available that outlines risk factors for altitude illness specifically in children. Table 3 contains possible risk factors for altitude illness inferred from a few pediatric and some adult studies. 1.3 Symptoms and signs of acute altitude illness
in children. At all ages (children and adults) the symptoms of altitude illness are nonspecific and can be confused with unrelated variables, such as intercurrent illness, dietary indiscretion, intoxication, or psychological factors associated with remote travel (Berghold and Schaffert, 1999). However, when ascending with children, it is wise to assume that such symptoms are altitude related and to take appropriate action, in addition to considering treatment for other possible causes. 
1. In older children (.8 years), it is assumed that altitude illness will present in much the same way as it does in adults.
2. Under 3 years of age, travel to any new environment may result in alterations of sleep, appetite, activity, and mood. Differentiating behavioral changes caused by travel alone from changes caused by altitude illness can be difficult. Because of variability in the developmental level of perception and expression in young
children, they are not reliable reporters of symptoms of altitude illness even when they can talk.
Symptoms may appear as nonspecific behavioral changes, rather than specific complaints of headache or nausea. The typical symptoms of acute mountain sickness in very young children include increased fussiness, decreased appetite and possibly vomiting, decreased playfulness, and difficulty sleeping. These symptoms usually begin 4 to 12 hours after ascent to altitude. A modification of the Lake Louise score has been
developed that assesses the nonspecific symptoms in very young children and may prove useful in the evaluation of preverbal children; see Appendix B (Yaron et al., 1998). However, at present this score has not been evaluated for routine use by parents or physicians in making decisions about the management of children at high altitude. The score has been validated as having high interobserver agreement when
used by parents, and it may be helpful in educating parents about the symptoms of AMS (Yaron et al., 2000).
3. Some older children, particularly those in the age range from 3 to 8 years, and children with learning or communication difficulties may also be poor at describing their symptoms, making altitude illness difficult to recognize. 
1.4 Prevention of acute altitude illness in children. There are no studies concerning the prevention of altitude illness in children; however, we assume that prevention principles in adults are also appropriate for children.
1.4.1. Graded ascent. Slow graded ascent, allowing time for acclimatization, is helpful. Anascent rate of 300 m per day above 2500 m and a rest day every 1000 m has been recommended, but it is not clear whether a more or less cautious recommendation is more appropriate for children. There are few data on how well children acclimatize to altitude in comparison to adults. Children were found to acclimatize at least as well if not better than adults in one report that recorded the change in heart rate and arterial oxygen saturation of
children 7 to 9 years of age and their adult parents during a slow graded ascent (Tuggy et al., 2000).
1.4.2. Drug prophylaxis to aid acclimatization in childhood usually should be avoided, as slower ascent achieves the same effect in most cases and minimizes the unnecessary use of drugs in childhood. In rare cases, when a rapid ascent is unavoidable, use of acetazolamide to aid acclimatization might be warranted in a child. Children with known previous susceptibility to AMS may benefit from prophylaxis to aid in acclimatization. Side effects do occur with acetazolamide, such as paresthesiae, skin rashes, and possible dehydration; thus use should not be encouraged. Sulfa allergy is a contraindication to acetazolamide use.
1.4.3. Education. Children and their carers should be acquainted with the symptoms of altitude illness and its management prior to altitude travel (above 2500 m). Parents should also know their children’s reactions during travel, irrespective of altitude, to be capable of differentiating high altitude illness from simple
travel symptoms. 
1.4.4. Emergency plan. An emergency contingency plan should be made by all groups traveling to a remote altitude location prior to travel so as to ensure evacuation of a sick member of the party if necessary. Part of the emergency plan should include provision of communications to facilitate evacuation. If a child is traveling to altitude, descent or access to oxygen should be possible immediately (within hours). Altitude sojourns when descent takes days or requires further ascent, prior to descent, should be avoided.
1.4.5. Group travel. School expeditions are a popular educational experience for older children. It is essential that organizations planning school group expeditions to (sleeping) altitudes above 2500 m plan an itinerary that allows graded ascent, rest days, easy descent, and a flexible itinerary in case of illness. Preexpedition p5. Medical and evacuation insurance (applies to all travelers).
1.5 Treatment of acute altitude illness in children. There are no studies of treatment of acute altitude illness in children. However, it seems appropriate to follow adult treatment algorithms with appropriate pediatric drug dosages as outlined below in Table 4. It may be prudent to be more cautious in managing children with acute mountain sickness and descend earlier after the onset of symptoms than would be the case for an adult, because the natural history of AMS in childhood is not well characterized. Descent, when possible, should involve minimal exertion, which might exacerbate symptoms, and the child should be carried where practical during descent.
2. Symptomatic high altitude pulmonary hypertension
Symptomatic high altitude pulmonary hypertension (SHAPH) includes acute exacerbations of pulmonary hypertension as well as the syndrome of subacute infantile mountain sickness (SIMS) or high altitude heart disease. 
Acute increases in pulmonary artery pressure have been observed in infants living or traveling to high altitude in association with intercurrent viral infections (Susan Niermeyer, unpublished observation). Treatment focuses on oxygen administration and descent. The subacute form of SHAPH occurs almost exclusively in infants (under 1 year of age) of lowaltitude ancestry who are continuously exposed to altitudes over 3000 m for more than 1 month (Wu and Liu, 1955; Khoury and Hawes, 1963; Sui et al., 1988; Wu, 1994). There may be ethnic differences in the risk of SHAPH. Incidence was 1% among Chinese infants at
3050 to 5188 m (Wu, 1994). In this condition, infants develop hypoxic pulmonary hypertension and consequent right ventricular cardiac failure. The presentation begins with poor feeding, lethargy, and sweating. Later, signs of heart failure such as dyspnea, cyanosis, cough, irritability, insomnia, hepatomegaly, edema,  and oliguria may become apparent. Management is different from acute mountain sicknesslanning should include the following:
1. Assessment of past medical history for each child.
2. Education of parents, staff, and children about altitude illness and other expedition health hazards.
3. Wilderness first aid training for staff members and preparation of an appropriate first aid kit.
4. Emergency and evacuation planning, including means of communication in an emergency.
5. Medical and evacuation insurance (applies
to all travelers).
1.5 Treatment of acute altitude illness in children.
There are no studies of treatment of acute altitude illness in children. However, it seems appropriate to follow adult treatment algorithms
with appropriate pediatric drug dosages as
outlined below in Table 4.
It may be prudent to be more cautious in
managing children with acute mountain sickness and descend earlier after the onset of
symptoms than would be the case for an adult,
because the natural history of AMS in childhood is not well characterized. Descent, when
possible, should involve minimal exertion,
which might exacerbate symptoms, and the
child should be carried where practical during
descent.
2. Symptomatic high altitude pulmonary
hypertension
Symptomatic high altitude pulmonary hypertension (SHAPH) includes acute exacerbations of pulmonary hypertension as well as the
syndrome of subacute infantile mountain sickness (SIMS) or high altitude heart disease.
Acute increases in pulmonary artery pressure
have been observed in infants living or traveling to high altitude in association with intercurrent viral infections (Susan Niermeyer, unpublished observation). Treatment focuses on
oxygen administration and descent. The subacute form of SHAPH occurs almost exclusively in infants (under 1 year of age) of lowaltitude ancestry who are continuously
exposed to altitudes over 3000 m for more than
1 month (Wu and Liu, 1955; Khoury and
Hawes, 1963; Sui et al., 1988; Wu, 1994). There
may be ethnic differences in the risk of SHAPH.
Incidence was 1% among Chinese infants at
3050 to 5188 m (Wu, 1994). In this condition,
infants develop hypoxic pulmonary hypertension and consequent right ventricular cardiac
failure. The presentation begins with poor feeding, lethargy, and sweating. Later, signs of
heart failure such as dyspnea, cyanosis, cough,
irritability, insomnia, hepatomegaly, edema,
and oliguria may become apparent. Management is different from acute mountain sickness and is directed at control of congestive cardiac failure and reversal of pulmonary hypertension.
Treatment consists of administration of oxygen, pharmacologic diuresis, and urgent descent.

3. Sudden infant death syndrome (SIDS)
It is unclear whether exposure to high altitude invokes an increased risk of SIDS as there are conflicting reports (Barkin et al., 1981; Getts and Hill, 1982; Kohlendorfer et al., 1998). The prone sleeping position is an important cofactor at altitude as well as at sea level (Kohlendorfer et al., 1998). As at sea level, the risk of
SIDS may be reduced by always laying the infant to sleep on the back and avoiding passive exposure to tobacco smoke (Wisborg et al., 2000). The possibility of an association warrants careful consideration of an ascent to altitude with a young (, 1 year old) infant. There is also a theoretical risk and some evidence that
exposure to altitude may interfere with the normal respiratory adaptation that occurs following birth (Niermeyer, 1997; Parkins et al., 1998).
4. Cold exposure
Infants and small children are particularly vulnerable to the effects of cold because of their large surface area to volume ratio. The child who has to be carried during a hike is not generating heat through muscle activity and is at risk of hypothermia. Adequate clothing is essential to prevent misery, hypothermia, and frostbite. The committee is aware of a number of cases of frostbite of extremities, including those necessitating amputations (unpublished observations, S. Kriemler; unpublished observations, J.A. Litch).
5. Sun exposure 
Reflection from snow and a thinner atmospheric layer at high altitude make the risk ofsolar ultraviolet radiation burns more likely than at sea level. Children are more likely to burn than adults if exposed to excess sun. Appropriate sun-block creams (UVA and B, SPF $ 30, applied before sun exposure), hats and
longsleeves, and goggles are required to prevent sunburn or snowblindness.
6. Other factors to consider when traveling in the altitude environment with children Traveling with children can be very rewarding for both parents and children alike. For many parents who carry their children into the
mountains, the trip is an opportunity to relax away from their normal daily activities. However, a number of factors should be considered that may improve the enjoyment of such travel for the children and parents (Berghold and Moravec, 1994). 
1. Boredom. Young children typically have a short attention span and will easily become bored after traveling relatively short distances. A stimulating itinerary should be carefully chosen.
2. Physical ability. Estimates of distances that young children might be expected to walk (at sea level) have been made (Gentile and Kennedy, 1991), but these should only be used as guidelines that may be adjusted for each individual child. It should be emphasized that children should only walk as long as they want to.
3. Food. Some young children may be very poorly adaptable to changes in circumstances and refuse unfamiliar food. It is helpful to try foods out prior to altitude travel when possible. It is important to ensure an adequate food and liquid intake. 
4. Hygiene. In remote treks, traveling with young infants may be particularly stressful for parents trying to maintain appropriate hygiene for their child.
5. Intercurrent illness. Gastroenteritis is probably no more common among child travelers than among adults. Children are more prone to develop severe, life-threatening dehydration with gastroenteritis, and supplies to make a safe oral rehydration solution should be part of every medical kit.
7. Children with preexisting illness

Children with certain underlying chronic medical conditions may be at increased risk of developing either an exacerbation of their chronic illness or an illness directly related to altitude, such as HAPE. Few to no data exist for determining the risk for specific medical conditions such as cystic fibrosis or chronic lung disease of prematurity (bronchopulmonary dysplasia). However, by first possessing a knowledge of known risk factors for the development of altitude-related illnesses and then assessing how each individual child’s condition may affect his or her cardiopulmonary physiology in a hypoxic environment, it may be possible to determine the relative risk of developing complications at altitude. For instance, both a relative lack of increased minute
ventilation at altitude and pulmonary vascular overperfusion, such as is seen in individuals who lack a pulmonary artery, are risk factors for the development of HAPE (Matsuzawa et al., 1989; Selland et al., 1993; Sebbane et al., 1997).
Therefore, it is logical to believe that children with congenital heart defects resulting in overperfusion of the pulmonary vascular bed, such as atrial and ventricular septal defects, unilateral absence of a pulmonary artery, and patent ductus arteriosus, would be at increased risk for the development of altitude-related illnesses like HAPE. Similarly, children who have significant lung disease secondary to premature birth or cystic fibrosis and have elevated PaCO2 levels at sea level may not be able to increase their minute ventilation when stressed by altitude and thus be at risk for illness at altitude. Children with Down syndrome have a high incidence of both obstructive apnea and hypoventilation, as well as congenital heart defects resulting in increased pulmonary blood flow. Perhaps these physiologic abnormalities contributed to the development of HAPE in children with Down syndrome at relatively low altitudes (Durmowicz, Pediatrics 2001, in press).
Children with noncardiopulmonary disorders may also be at increased risk for the development of illness at altitude depending on how the disorder responds to the stresses of al-titude. For instance, a child with cortisol deficiency secondary to adrenogenital syndrome developed HAPE at moderate altitude, as did two children with cancer who had recently finished chemotherapy (unpublished observations, A.G. Durmowicz). New onset or recurrent seizures in children who are no longer on medication may occur at as low as 2700 m (unpublished observation, P.H. Hackett). In addition, children with sickle cell anemia appear to be at increased risk for sickling crises at altitude (Mahony and Githens, 1979).
Above all, if parents decide to travel to altitude with children with chronic medical conditions, special planning to ensure adequate supplies and for expedient evacuation is essential. This likely means limiting travels to
more developed altitude destinations, rather than isolated backcountry trips.
8. Statement on special considerations for ascent to altitude with children

1 There are no data about safe absolute altitudes for ascent in children.
2. The risk of acute altitude illness is for ascents above about 2500 m, particularly sleeping above 2500 m.
3. Intercurrent illness might increase the risk of altitude illness.
4. Effects of longer-term (weeks) exposure to altitude hypoxia on overall growth and brain and cardiopulmonary development are unknown.
8.1 Location of travel. Travel to high altitude in mountain and ski resorts in industrialized countries with easy and rapid access to medical care should be considered differently from remote travel in isolated mountain ranges and areas without access to a high level of medical sophistication.
1. Most mountain tourist sites and ski resorts in industrialized countries are located at or below about 3000 m, and a majority of travelers to these sites will sleep at about 3000 m or less.
Acute mountain sickness is common at this altitude, and there is probably a small risk of serious altitude illness. Once recognized, altitude illness is effectively managed with oxygenand/or descent in most cases. Ascents during tourist activities (cable car rides, travel on mountain roads, and ski trips) to altitudes
higher than the resort location, about 4000 m, are usually brief (hours) and probably carry minimal additional risk. Longer trips above 3000 m on foot or horseback should be undertaken with slow graded and cautious ascent to reduce the possibility of altitude illness.
2. Ascents made in remote mountain locations without rapid access to medical care should be undertaken with greater caution. Ascents with sleeping altitudes at or below 3000 m carry a low risk of serious altitude illness; but when HAPE or HACE occurs, management can be more difficult than in developed areas.
Higher ascents in this context should be undertaken with slow-graded ascent, rest (acclimatization) days, and careful emergency planning.
8.2 Age of the child
1. Altitude illness is especially difficult to recognize in preverbal children (,3 years), who cannot report classic symptoms of mountain sickness. Similarly, some children from 3 to 8 years may be good at reporting symptoms, but extra caution is required for the younger children in this age range and for children with
learning difficulties who will be poor at expressing their experience of symptoms of acute altitude illness. Older children (.8 years) have usually reached the developmental level necessary to report these symptoms.
2. Many preverbal children travel to resorts at 3000 m in North American mountain ranges without complications, but extra caution is required for higher ascents and for ascents in remote areas.
3. For infants in the first few weeks and months of life, there may be some additional theoretical concerns that exposure to over 2500m for more than a few hours may affect normal respiratory patterns (Parkins et al., 1998).
8.3 Length of altitude exposure
1. Ascents higher than 3000 m that are prolonged (.1 day) or require sleeping above 3000m increase the risk of acute mountain sicknessand should be undertaken cautiously with slow graded ascent, built-in rest days, and emergency planning.
2. In circumstances where the child is traveling above 2500-m altitude because of parental occupation and prolonged altitude residence is anticipated, slow graded ascent as described in Section 1.4 should be undertaken. For infants (,1 year) planning to reside permanently at altitude, some authorities recommend delaying ascent to altitude until beyond the first year of life because of the slight risk of SIMS above 3000 m. This is usually impractical if parental separation is to be avoided. Therefore, after a careful physical exam before ascent and initial acclimatization to high altitude, the infant should be followed closely with respect to
growth percentiles; pulse oximetry may be useful, especially during sleep, and the ECG should be monitored periodically for the development of right ventricular hypertrophy.
9. Conclusion
Wilderness travel with children is a rewarding experience for parents and carers when undertaken with adequate preparation. Ascent to altitude adds an extra dimension to such wilderness travel and must be carefully considered. Unfortunately, there are few data to direct guidance, but consideration of a few pediatric studies and extrapolation from adult data provide a framework for safe practice. The consensus view described here provides conservative recommendations that should be helpful for physicians who are required to offer advice about ascent to high altitude with children.


第二篇參考資料 What is high-altitude pulmonary edema in children?(連結在此) 

這一篇論文是美國科羅拉多兒童醫院發表的. 剛稍微搜尋一下該醫院的背景, 裡面的醫師看起來都很厲害
Gwendolyn Kerby, MD Pulmonology - Pediatric
Oren Kupfer, MD Pulmonology - Pediatric, Pediatrics
Steve Abman, MD Pulmonology - Pediatric, Pediatrics
Stephen Hawkins, MD Pulmonology - Pediatric, Pediatrics, Sleep Medicine
什麼是小兒高海拔肺水腫?
肺水腫患者, 肺部會充斥液體, 通常發生在高海拔, 但少數在中海拔發病
患者會呼吸困難, 一開始乾咳, 隨病情嚴重會出現痰液, 也可能會咳血, 患者氧氣濃度通常很低.
What is high-altitude pulmonary edema in children?
High-altitude pulmonary edema (HAPE) is a condition in which a child's lungs fill with fluid at high elevation (or rarely, moderate elevation). Children complain of trouble breathing, and they have a cough that starts out dry and becomes wet. They may also cough up blood. Their oxygen levels are also low.
在這裡直接將HAPE分三種(uptodate說兩種, 不含小兒高海拔肺水腫)
There are three types of HAPE:
上面兩種, "典型HAPE"與"再返HAPE"(不知道怎麼翻譯比較好), 在uptodate 上面有介紹, 
Classic HAPE occurs in children who live at a lower elevation and develop symptoms after traveling to high elevation.
Re-entry HAPE occurs in children who live at high elevation, travel to low elevation and then develop symptoms after they return home.
High-altitude resident pulmonary edema (HARPE) occurs in children who live at high elevation and develop symptoms without a change in elevation.
HAPE can happen more than once in many children. At Children's Hospital Colorado, we have vast experience helping children who are affected by altitude and can provide helpful advice on preventing it in the future.

What causes high-altitude pulmonary edema?
There is less oxygen at high altitude, which causes blood vessels in the lungs to constrict or tighten. This leads to fluid leaking into the lungs.

Who gets high-altitude pulmonary edema?
HAPE appears to run in some families and is more common in males before puberty. Children with certain underlying heart or lung conditions, such as obstructive sleep apnea, pulmonary hypertension, atrial septal defect and ventricular septal defect, are more likely to develop HAPE. Respiratory infections often trigger HAPE in children.

 

What are the signs and symptoms of high-altitude pulmonary edema?
Children may have one or more of the following signs and symptoms:

Cough that starts out dry and becomes wet
Coughing up blood
Shortness of breath
Blue or purple lips
What tests are used to diagnose high-altitude pulmonary edema?
Typically, we do a chest X-ray to confirm pulmonary edema and to evaluate for other lung diseases. A pediatric chest X-ray is a test that provides a picture of a child's heart, lungs and bones in the chest. Less commonly, a chest ultrasound may be done at some of our locations. A chest ultrasound uses sound waves to produce pictures of the inside of the chest.

How do we diagnose high-altitude pulmonary edema in children?
Our providers diagnose a child with HAPE when they have signs and symptoms of pulmonary edema and they have had a recent change to high elevation, or they live at a high elevation and then develop symptoms.

How is high-altitude pulmonary edema treated?
We treat HAPE by giving your child supplemental oxygen and/or moving them to a lower elevation. Sometimes medicines can help lower blood pressure in the blood vessels of the lungs. It is also important that we evaluate your child for any underlying heart disease. Our experts in high-altitude pulmonary edema can help determine if your child needs any additional testing or treatments.

Prevention of HAPE includes a slow ascent to high elevation, using oxygen during sleep at home and/or medicines.

Why choose Children's Colorado for treatment of high-altitude pulmonary edema?
Our Breathing Institute and Heart Institute are among the best at what they do and have multiple experts who can treat high-altitude pulmonary edema. We have pediatric pulmonologists and pediatric cardiologists who have specialized expertise in treating high-altitude pulmonary edema. These pediatric specialists often partner together to take care of children with HAPE, ensuring they receive the most complete care. We also conduct ongoing research to better understand HAPE.

野外與登山醫學--- 2017 High Altitude Pulmonary Edema (HAPE)

另一篇重複發文. 但中文翻譯稍微不同. 懶得改了. 附上筆記連結

Altitude Illness, Pulmonary Syndromes, High Altitude Pulmonary Edema (HAPE)
Jacob D. Jensen; Andrew L. Vincent.

Author Information
Last Update: October 10, 2017.

HAPE是缺氧導致的非心因性肺水腫, 屬於臨床診斷, 特徵是疲倦, 呼吸困難, 運動時乾咳, 如果不治療, 會進展成休息時呼吸困難, 發紺, 死亡率 50%
Introduction
High Altitude Pulmonary Edema (HAPE) is a fatal form of severe high-altitude illness. HAPE is a form of noncardiogenic pulmonary edema that occurs secondary to hypoxia. It is a clinical diagnosis characterized by fatigue, dyspnea, and dry cough with exertion. If left untreated, it can progress to dyspnea at rest, rales, cyanosis, and a mortality rate of up to 50%.

HAPE通常發生於海拔 2500 公尺以上, 但也有2000公尺發生的案例, 危險因子包括, 個體因素, 到達海拔, 快速上升, 男性, 使用安眠藥, 過度攝取鹽分, 低溫, 高強度體力活動, 其他前置因素會造成肺血流上升, 肺高壓., 肺血管反應增加, 開放性卵圓窗, 會有更高的HAPE發生率
Etiology
Along with other illnesses related to altitude, HAPE occurs above 2500 meters but can occur at altitudes as low as 2000 meters. Risk factors include individual susceptibility due to low hypoxic ventilatory response (HVR), the altitude attained, a rapid rate of ascent, male sex, use of sleep medication, excessive salt ingestion, ambient cold temperature, and heavy physical exertion. Preexisting conditions such as those leading to increased pulmonary blood flow, pulmonary hypertension, increased pulmonary vascular reactivity, or patent foramen ovale may have a higher predisposition towards the development of HAPE.

HAPE嚴重度決定於多項因素, 包括海拔, 初步認知, 處置, 尋求醫療協助, 在海拔 4500 公尺的發生率 0.6%-6%, 在海拔 5500 公尺的發生率高達 60%. 個人體能無法避免HAPE發生. (level of fitness.) 經過治療的死亡率 11%, 未治療死亡率 50%, 大約 50% HAPE患者會同時罹患AMS,. 14% 同時罹患HACE. 
Epidemiology
The severity of HAPE will depend on multiple factors including altitude, initial recognition and management, and access to medical care. At 4500 meters the incidence is 0.6% to 6%, and at 5500 meters the incidence is 2% to 15%, with faster ascent time correlating to a higher incidence. Those with a prior incidence of HAPE have a recurrence rate as high as a 60%. One’s level of fitness is not proven to be a protective factor. Mortality rate, when treated, can be as high as 11% and as high as 50% when untreated. Up to 50% of cases may have concomitant acute mountain sickness (AMS), and up to 14% will have concomitant high altitude cerebral edema (HACE).

Pathophysiology
The development of HAPE occurs as a response of the pulmonary vasculature to hypoxia. At altitude, the body responds to hypoxia by hyperventilation. This is known as the hypoxic ventilatory response (HVR). This response varies between individuals and has a genetic component. High altitude adaptation is an interesting phenomenon that regularly applies to individuals living at altitude for long periods of time but is not usual for those visiting altitude. Understanding the principles of tissue oxygen delivery, however, is useful when considering the effects and adaptations of those coming from higher barometric pressures to the lower pressures of high elevation. The concentration of oxygen in 1 liter of air at sea level is 21%. This concentration is the same at 4000 meters (~13,200 feet), but due to the decreased barometric pressure at this altitude, only 63% of the number of available oxygen molecules remain as compared to sea level. Thus, to adequately deliver oxygen to the tissues, particularly those that are most in need of oxygen for aerobic metabolism (brain, heart, lungs, kidneys), certain adaptations must occur.

There are four potential adaptations to overcome the constraints of high altitude hypoxia: (1) resting ventilation, (2) hypoxic ventilatory response, (3) oxygen saturation of arterial hemoglobin, and (4) hemoglobin concentration. Studies of populations in the Andes and Tibetian ranges and ranges have shown different adaptive changes between groups despite being at the same altitude. Those from Tibet had mean 0.5 standard deviations above that of the Aymara people of the Andes for the first two traits and a full standard deviation below for the latter two traits. This research suggests a genetic predisposition to how different groups of people at the same altitude may adapt to high altitude stress. For those traveling to a high altitude for a short period, minute-ventilation tends to be the mechanism by which trekkers from low altitude will acclimate. In general, it takes as much as 1 to 2 weeks for erythropoietin levels to increase enough to cause hematopoiesis and increased circulating hemoglobin. As one enters higher elevations, minute-ventilation increases almost immediately and respiratory alkalosis ensues. This causes a shift in the oxygen-dissociation curve to the left (increased affinity of oxygen by hemoglobin). In response to this mechanism, the kidneys begin increasing proton reabsorption which stabilizes the blood pH. RBC 2,3-DPG levels which begin to increase on days 2 and 3. Then, the Hgb-O2 dissociation curve shifts to the right (decreased affinity for O2 by hemoglobin). This allows for a more adequate delivery of oxygen to the tissues, particularly muscle tissues that may be under greater levels of stress due to exertion with climbing and/or trekking. If the HVR is blunted, due to genetic predisposition or sedatives, it will lead to further hypoxia causing a non-uniform, exaggerated hypoxemic pulmonary vasoconstriction (HPV). This pulmonary vasoconstriction then results in increased perfusion to affected alveoli, causing increased hydrostatic stress/pressure and thus increased mechanical stress on the blood-gas barrier. Damage to the blood-gas barrier results in increased capillary permeability and subsequent non-uniform pulmonary edema. This edema formation impedes oxygen transport, resulting in more widespread and worsening HPV. Sympathetic stimulation and circulating vasoconstrictors from the HPV response result in vasoconstriction, worsening pulmonary hypertension, and increasing capillary pressures. If an individual lacks innate adaptation to these organ level changes or the condition is not recognized and treated, the disease condition will persist and continue to worsen.

HAPE典型發作在到達高海拔的第2-5天, 開始是不知不覺的乾咳, 體力下降, 胸痛, 運動時呼吸困難, 如果不治療, 可進展成休息時呼吸困難, 嚴重的運動呼吸困難. 咳嗽可能逐漸變成咳出粉紅色泡沫痰. 胸部理學檢查可發現囉音或哮鳴, 中心型發紺, 呼吸快速, 低血氧, 通常SpO2會低於該海拔預期數值的 10%, 但病患臨床表現會比其實際的缺氧情況或SpO2來的好. SpO2 氧氣濃度通常 40%-70%.

History and Physical
HAPE typically occurs 2 to 5 days after arrival at altitude. It has an insidious onset with a non-productive cough, decreased exercise tolerance, chest pain, and exertional dyspnea. Without treatment, it can progress to dyspnea at rest and severe exertional dyspnea. A cough may become productive of pink and frothy sputum or frank blood. The patient also may have rales or wheezes, central cyanosis, tachypnea, and/or tachycardia. SpO2 is often 10% less than expected for altitude, and the patient often will appear better than expected given their level of hypoxemia and SpO2 value, which typically resides around 40% to 70%.

Evaluation
HAPE's clinical diagnosis would include at least two of the following symptoms or complaints: chest tightness or pain, cough, dyspnea at rest, and decreased exercise tolerance. It also would have two of the following exam findings: central cyanosis, rales/wheezes, tachycardia, and tachypnea. If available, CXR may show patchy alveolar infiltrates with normal-sized mediastinum/heart, and ultrasound may show B-lines consistent with pulmonary edema. ECG may show signs of right axis deviation and/or ischemia. In a patient with infiltrates on CXR, rapid correction of clinical status and SpO2 with supplemental oxygen is pathognomonic of HAPE. Even if available, labs are of limited utility, and the clinician should always consider concomitant AMS and/or HACE.

Treatment / Management 治療: 下降1000公尺. 或下降至症狀改善. 下降過程減少患者的運動量(減輕背包,背負下山). 如果有氧氣可以給氧, 可延緩惡化, 但下降仍是主要的治療手段. 氧氣攜帶量如果充足, 將血氧濃度維持在 90% 以上. 攜帶式加壓艙在無法下降的情況可考慮使用, 但需要有人持續在一旁照料, 某些狀況可能不太適合: 嘔吐, 幽閉空間恐懼症, 神智改變(例如同時罹患HACE), 當病患出加壓艙也有可能再次惡化, nifedipine 可降低肺血管收縮, 改善症狀, 可作為輔助治療, 但如果可以下降, 或者有充足的氧氣可供使用, 不宜將 nifedipine 作為唯一的治療方式. 沒有nifedipine也可以考慮使用 威而鋼或犀利士. 至於 acetazolamide, 乙型作用劑(氣管擴張劑), 利尿劑在臨床上沒有角色. (2013年NEJM說其他種類利尿劑無效.可能有害. 丹木斯雖未被證實能治療肺水腫, 但如果沒有不能服用的理由, 丹木斯可加速高度適應, 可考慮同時服用)

The mainstay of treatment is to descend 1000 meters or until there is a resolution of symptoms with the descent. During the descent, it is important to minimize exertion as exertion may increase hypoxemia from metabolic demands of the body and worsen an individual’s condition. If available, a trial of oxygen therapy may ameliorate symptoms and help temporize the patient if the descent is technically difficult or delayed. That said, the mainstay of treatment remains descent, regardless of oxygen availability. Supplemental oxygen via a high-flow nasal cannula and facemask titrated to Sp02 greater than 90% is a reasonable alternative when available. Portable hyperbaric chambers also may be used when descent is not possible, but these typically require constant care and may be difficult for individuals experiencing nausea or vomiting, claustrophobia, or altered mental status from concomitant AMS/HACE. There also exists the risk of recurrence of symptoms after exiting from the chamber. Nifedipine improves symptoms as an adjunct by decreasing pulmonary vasoconstriction but should not be used as the sole therapy if oxygen or descent are options. Phosphodiesterase inhibitors may be used to help to decrease pulmonary artery and capillary pressure through vasodilation if nifedipine is unavailable. There is no clinically proven role for acetazolamide, B-agonist, or diuretics.

Pearls and Other Issues
Individuals may consider resuming ascent at an appropriate rate once symptoms resolve and they no longer require oxygen or vasodilator therapy and have an increased exercise tolerance compared to symptom onset. Clinicians also should consider nifedipine, PDE inhibitors, or salmeterol as prophylaxis for those with a prior incidence of HAPE.