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.