野外與登山醫學-2014 WMS Practice Guidelines 3 高海拔疾病預防及治療 3

1. 高山病及高海拔腦水腫預防 http://blog.xuite.net/ymmcc/twblog/540135871
2. 高山病及高海拔腦水腫治療 http://blog.xuite.net/ymmcc/twblog/540164931
3. 高海拔肺水腫預防 http://blog.xuite.net/ymmcc/twblog/540171169
4. 高海拔肺水腫治療 http://blog.xuite.net/ymmcc/twblog/540177927
5. 同時罹患HACE及HAPE的治療 http://blog.xuite.net/ymmcc/twblog/540188730

2014 Wilderness Medical Society Practice Guidelines 高海拔疾病預防及治療 第三節 高海拔肺水腫

HAPE 高海拔肺水腫，雖然有些預防治療方式跟 AMS/HACE 雷同，但兩類病生理機轉截然不同，處置方式也有差異

High Altitude Pulmonary Edema

Information on the epidemiology, clinical presentation, and pathophysiology of HAPE, the majority of which comes from studies in adults, is provided in several extensive reviews.10,11,41,42 Although some of the prophylactic and therapeutic modalities are the same for HAPE as for AMS and HACE, important differences in the underlying pathophysiology of the disorder dictate different management and treatment approaches.

HAPE預防  PREVENTION

Potential preventive measures for HAPE include the following.

1. Gradual ascent 逐漸上升，雖然沒有研究評估是否限制睡眠海拔上升速率能預防 HAPE，但上升速率與疾病發生率有明確關係. 

(高度適應中的分次上升 staged ascent 則是指在中海拔 2200-3000 公尺 待 6-7 天)

No studies have prospectively assessed whether limiting the rate of increase in sleeping elevation prevents HAPE; however, there is a clear relationship between the rate of ascent and disease incidence.14,43,44 Recommendation Grade: 1C.

2. Nifedipine 鈣離子阻斷劑. 台灣常見的是 adalat 5mg , atanaal 5mg, coracten 20mg. 

在容易罹患 HAPE 的人使用 nifedipine 預防，建議劑量長效型 30mg, 一天吃兩次

A single randomized, placebo-controlled study45 and extensive clinical experience have established a role for nifedipine in HAPE prevention in susceptible individuals. The recommended dose is 30 mg of the extended-release preparation administered twice daily. Recommendation Grade: 1A.

3. Salmeterol 乙型作用劑，吸入性長效型乙型作用劑 salmeterol 對於容易罹患HAPE 的人能降低 50％的發生率，高劑量使用會有副作用 (125ug/一天兩次)，該藥物在高海拔的臨床經驗不多，因此 salmeterol 不建議單獨使用，需搭配 nifedipine 使用

In a single randomized, placebo-controlled study, the long-acting inhaled β-agonist salmeterol decreased the incidence of HAPE by 50% in susceptible individuals.46 Very high doses (125 μg twice daily) that are often associated with side effects were used in the study. Clinical experience with the medication at high altitude is limited. As a result, salmeterol is not recommended as monotherapy but may be considered as a supplement to nifedipine. Recommendation Grade: 2B.

4. Tadalafil 犀利士，一項研究對於容易罹患 HAPE 的人，給予 10mg 每天吃兩次能預防 HAPE，但研究規模小，且兩名受測者罹患嚴重AMS，無臨床試驗比較犀利士與 nifedipine 比較  

In a single randomized, placebo-controlled trial, 10 mg twice daily of tadalafil was effective in preventing HAPE in susceptible individuals.47 The number of individuals in the study was small, and 2 subjects experienced incapacitating AMS. Clinical experience with tadalafil is lacking compared with nifedipine. As a result, further data are necessary to validate these results. Recommendation Grade: 1C.

5. 類固醇 地塞米松 Dexamethasone。在易罹患 HAPE 的人，使用類固醇也有預防 HAPE 效果，機轉不明，臨床經驗不足

In the same study that assessed the role of tadalafil in HAPE prevention, dexamethasone (16 mg/d in divided doses) was also shown to prevent HAPE in susceptible individuals. The mechanism for this effect is not clear, and there is very little, if any, clinical experience using dexamethasone for this purpose. Further data are necessary to validate this result. Recommendation Grade: 1C.

6. 丹木斯 Acetazolamide，可加速高度適應，應該能預防各類型的高海拔疾病，在動物實驗及人類實驗可減少低氧性肺血管收縮，但針對HAPE預防尚未有資料，臨床觀察顯示丹木斯也可能預防 reentry HAPE，這是指居住在高海拔的兒童，到低海拔地區旅遊，快速回到住所之後出現的HAPE

Because acetazolamide hastens acclimatization, it should be effective at preventing all forms of acute altitude illness. It has been shown to blunt hypoxic pulmonary vasoconstriction in animal models48,49 and in a single study in humans,50 but there are no data specifically supporting a role in HAPE prevention. Clinical observations suggest acetazolamide may prevent reentry HAPE, a disorder seen in children who reside at high altitude, travel to lower elevation, and then develop HAPE upon rapid return to their residence. Recommendation Grade: 2C.

7. Preacclimatization and staged ascent，高度適應、分次上升。無研究證實是否對HAPE預防有效果。Staged ascent 這裡作法是在中海拔 2200 公尺停留 7 天，能緩解低氧造成的肺動脈壓上升，這是HAPE的關鍵病理表現。但在中海拔需要多久的時間和強度仍未明，也無研究評估是否對容易罹患HAPE的人有效果。

雖然高度適應和分次上升風險小，但對於高海拔遊客的可行性是主要考量(很多既定安排的旅程無法實現)，目前仍無法針對高度適應及分次上升給予建議。

No study has examined whether preacclimatization strategies are useful for HAPE prevention. Staged ascent, with 7 days of residence at moderate altitude (approximately 2200 m), has been shown to blunt the hypoxia induced increase in pulmonary artery pressure, a key feature of the pathophysiology of HAPE.31 However, uncertainty remains as to the magnitude and duration of moderate altitude exposure necessary to yield benefit, and no study has specifically investigated whether the strategy is of benefit in known HAPE-susceptible individuals. Although the risks of preacclimatization and staged ascent are likely low, feasibility is a concern for many high altitude travelers. No specific recommendations regarding the appropriate preacclimatization or staging regimen can be made at this time. Recommendation Grade: 2C.

總結HAPE預防，個體對於高海拔的生理反應與高度適應各有差異，以下建議雖然多數時候有效，但並不保證一定成功

1. 針對HAPE主要的預防方式是，上升要緩慢，比照AMS和HACE預防方式

2. 只有先前曾罹患HAPE的人才需要使用藥物預防HAPE，nifedipine 是首選藥物，在上升前一天就要開始使用，持續到高度下降，或在目標海拔超過四天。如果上升速率超過建議速率，在目標海拔持續使用藥物七天
3. 如果旅遊途中經過高海拔，之後開始下降，下降的時候就可以停藥

4. 關於犀利士和類固醇預防HAPE的建議仍需更多研究

5. 丹木斯是預防HAPE合理的藥物，臨床經驗也支持，但尚缺研究證實

6. salmeterol 僅用於輔助 nifedipine 預防 高危險患者罹患 HAPE

Suggested approach to HAPE prevention

As noted earlier, because the physiologic responses to high altitude and rates of acclimatization vary considerably between individuals, the recommendations that follow, while generally effective, will not guarantee successful prevention in all high altitude travelers. A gradual ascent profile is the primary recommended method for preventing HAPE; the recommended ascent rate noted above for AMS and HACE prevention also applies with HAPE prevention. Drug prophylaxis should only be considered for individuals with a prior history of HAPE, especially multiple episodes, and nifedipine is the preferred option in such situations. It should be started the day before ascent and continued either until descent is initiated or the individual has spent 4 days at the target elevation. The duration of use at the target elevation should be extended to 7 days if the individual ascended faster than recommended ascent rates. 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. Further research is needed before tadalafil or dexamethasone can be recommended for this purpose. Acetazolamide is a rational choice for HAPE prevention and clinical experience supports this, but data are lacking. Salmeterol should only be considered as a supplement to nifedipine in high-risk individuals with a clear history of recurrent HAPE.