野外與登山醫學: Summary of WMS Practice Guidelines 2024 Update 高海拔疾病預防-診斷-治療

2025-10-31 10:09AM

寫在前面, WMS高海拔疾病預防診斷治療指引是給醫師看的. 不是寫給一般民眾. 我會儘量將內容簡化讓大家能看懂

Summary of Wilderness Medical Society Practice Guidelines for the Prevention, Diagnosis and Treatment of Acute Altitude Illness: 2024 Update
George RodwayAndrew Luks－　2024年7月8日－Volume 41, Issue 3

注意. 有些文獻的風險等級是用於預測AMS發生機率. 這張圖是預測高海拔疾病發生率. 

(高海拔疾病包含AMS; AMS沒有包含其他高海拔疾病)

圖一 fig 1 

英文名詞/縮寫及中文翻譯

AAI= acute altitude illness 急性(高)海拔疾病

HAI=high altitude illness 高海拔疾病

AMS= acute mountain sickness 急性高山病

HACE=high altitude cerebral edema 高海拔腦水腫　

HAPE =high altitude pulmonary edema 高海拔肺水腫

高海拔疾病. 在不同文獻出現不同稱呼. 但都是指同一個疾病,  acute altitude illness 等於 high altitude illness 等於 altitude illness. 

建議大家在翻譯成中文時, 將AMS翻譯為急性高山病, 不要翻成急性高山症. 高海拔疾病儘量不要說成高山症. 原因是很多民眾會將高山症與急性高山症畫上等號. 導致用威而鋼預防AMS的謬誤

高山症等於AMS+HACE+HAPE+其他

高海拔疾病=高山症 high altitude illness 

高山症不等於急性高山症AMS

高山症不等於急性高山病AMS

下面中文使用GOOGLE自動翻譯

概論

前往海拔2500公尺以上的地區旅行有發生高海拔疾病AAI(acute altitude illness)的風險，包括AMS, HACE, HAPE. 雖然未適應高山環境的人在攀登到海拔2500公尺以上時會面臨高海拔疾病的風險，但由於個體對高海拔疾病的差異很大，在較低海拔也可能出現AAI。

為了指導臨床醫生並傳播最佳實踐知識，荒野醫學會（WMS）召集了一個專家小組，制定了基於循證醫學的急性高原病預防、診斷和治療指南。本文介紹了預防和治療方法，並針對每種急性高原症提出了建議。

AMS和HACE
從臨床角度來看，高海拔腦水腫是AMS的一種極其嚴重的類型；因此，可以同時採取針對這兩種疾病的預防和治療措施。

(可視為同一種疾病. AMS是早期. HACE是晚期)

AMS急性高山病/HACE高海拔腦水腫的預防
建議：預防AMS和高海拔腦水腫的方法應取決於前往高海拔地區個人的風險狀況（圖1）。首要任務是確保逐步上升到目標海拔。旅行者可以透過在中等海拔地區過夜來降低風險。例如，居住在海平面的居民前往海拔2800公尺以上的科羅拉多州度假區，可以在丹佛（海拔1600公尺）過夜。如果由於各種後勤因素導致旅行者無法逐步上升，則可以考慮藥物預防。在低風險情況下，通常不需要預防性藥物，但在中高風險情況下，除了逐步上升之外，還應考慮使用藥物（圖1）。在海拔3000米以上地區旅行時，每日睡眠海拔升高幅度不應超過500米，並且應每3-4天安排一天休息日（即不攀登至更高海拔的睡眠地點）。

丹木斯(乙醯唑胺)：丹木斯在預防急性高山病方面具有確切療效。對磺胺類藥物過敏者服用丹木斯有誘發過敏反應的風險，儘管這種風險極低。過去對磺胺類藥物有過敏性休克史或有史蒂文斯-約翰遜症候群病史者禁用丹木斯。丹木斯應在登山前一天開始服用，但即使在登山當天開始服用，仍然有效（表1）。

類固醇(地塞米松) Dexamethasone：地塞米松不像丹木斯那樣有助於適應高山環境，但它在預防AMS方面具有確切療效。只有在極高風險的情況下，例如軍事人員或搜救人員被空運到海拔 3500 公尺以上並立即進行體力活動時，才可考慮使用高於表 1 中建議劑量（每 6 小時 4 毫克）的劑量。如果使用超過 5-7 天，地塞米松應在一週內逐漸減量，而不是突然停藥。不建議兒童使用地塞米松預防AMS。地塞米松應在攀登前一天開始服用，但即使在攀登當天開始服用，仍然有效。

(類固醇種類很多. 目前高海拔研究最常用的是Dexamethasone. 其他類固醇, 例如  prednisolone 也有少量文獻說有效. 但研究證據不充足. 無法做結論)

消炎止痛藥NSAID布洛芬：在快速攀登過程中，布洛芬不建議用於預防AMS，其療效不如丹木斯或地塞米松（表 1）。但是，對於不願服用乙醯唑胺或地塞米松，或對這些藥物過敏或不耐受的人，可以使用布洛芬。

(非首選.不得以時可作為備用選項)

分階段攀登與預適應：專家小組不建議任何特定的預適應方案（即在高海拔旅行前反覆暴露於低氧環境）和分階段攀登方案（即在攀登至目標海拔前，先在中等海拔停留數日）作為預防AMS的手段。關於在低氧帳篷中進行常壓低氧暴露，只有在適當週數內定期進行足夠長時間（每天超過 8 小時）的暴露，才有可能帶來顯著的預適應益處。

其他選擇：

以下措施尚未被證實有效：

咀嚼古柯葉、

飲用古柯茶和其他古柯衍生產品；

「強制」或「過度」補水；

短期吸氧，例如前往氧吧或使用非處方氧氣輸送系統（透過吸入預充式小罐中的富氧氣體）；

其他非處方產品，例如粉末狀飲料沖劑、貼片和口服補充劑。

(利尿劑 furosemide 在2013年NEJM的高海拔疾病文獻中已經被剔除. 罹患HAPE的患者體內通常是脫水狀態. 因此利尿劑對於高海拔肺水腫無效. 且可能有害)

急性高山病/高海拔腦水腫(AMS/HACE) 的診斷
AMS的診斷是在非常特定的臨床背景下做出的，即未適應高海拔環境的低地居民在攀登至高海拔地區（通常高於 2500 公尺）後數小時至 3 天內出現不適症狀。診斷完全基於患者自述的症狀，因為身體檢查或實驗室檢查沒有特徵性發現。

AMS的症狀包括：頭痛、厭食、噁心、疲勞和頭暈。

根據更新後的路易斯湖AMS評分表（見表 2），這些指引強調頭痛在AMS診斷中的作用，而弱化睡眠障礙的重要性。

最佳的診斷方法是考慮旅行者的健康狀況和功能狀態。

在攀登至海拔高於 2500 公尺的地區後數小時至 3 天內感到不適和/或必須減少日常活動的人很可能患有AMS。

高海拔腦水腫 (HACE) 的診斷以腦病徵象(運動失調或神智改變)為先兆，包括共濟失調（通常是最早出現的臨床表現）和精神狀態改變。其他體徵包括冷漠、易怒、疲倦和無法自理，所有這些體徵都可能很輕微。未經治療的 HACE 可進展至昏迷。局部神經功能缺損並不常見，應考慮其他診斷。足跟到足尖行走可用於評估共濟失調，視乳頭水腫可確診為腦水腫。

建議的AMS/HACE 治療

方案：應注意排除症狀和體徵與 AMS 和 HACE 相似的疾病，例如腦血管意外、一氧化碳中毒、低血糖、低鈉血症、感染或創傷性腦損傷
。

高海拔肺水腫（HAPE ）的某些危急程度是根據對AMS的預測而定的，但兩種類型的AMS並不相同。任何程度的AMS或高海拔腦水腫（HACE）患者都應停止上升，並可能需要考慮下降，具體取決於病情嚴重程度和具體情況。 AMS患者症狀緩解後可恢復上升。如果症狀持續存在，切勿繼續上升或重新上升到先前達到的高度。對於任何疑似HACE患者，或儘管使用丹木斯或地塞米松治療，AMS症狀仍持續惡化的情況，都應開始下降。

對於中度至重度AMS/HACE，地塞米松被認為是比丹木斯可靠的藥物治療。如果下降不可行，也應使用補充氧氣或攜帶式高壓艙。

補充氧氣：如果條件允許，可透過鼻導管或面罩以足以緩解症狀的流量輸送氧氣，作為下降的合適替代方案。

當建議下降但不可行，或重症患者在下降過程中也應使用氧氣。血氧飽和度（SpO2）> 90% 通常足夠。

不應依賴短期使用非處方氧氣罐來達到此目的。

便攜式高壓艙：便攜式高壓艙可有效治療嚴重的高海拔疾病，但需要醫護人員持續照顧，且難以用於幽閉恐懼症或嘔吐的患者。

在許多情況下，患者病情可能會好轉，症狀緩解後即可協助撤離並下降。

在需要下降的情況下，使用便攜式高壓艙不應延誤下降。

丹木斯：應考慮使用丹木斯治療AMS（表 1）。

地塞米松：地塞米松是治療AMS非常有效的藥物。該藥物不能促進適應性訓練，因此應推遲進一步的上升，直到患者停藥且無症狀。大量的臨床經驗支持在 HACE 患者中使用地塞米松（表 1）。

高海拔肺水腫(HAPE) 

HAPE預防建議：

由於個體對高海拔的適應速度和生理反應差異很大，本文提出的上昇路線建議並不能保證所有高海拔旅行者都能預防 HAPE。

循序漸進的上昇路線是預防 HAPE 的主要方法；

上述針對AMS 和HACE 的預防建議也適用於 HAPE 的預防。

藥物預防僅適用於有 HAPE 病史的個體，尤其是多次發作者。

(不曾罹患 HAPE 的民眾不需要預防性服藥)

循序漸進的上升：上升速度與疾病發生率之間有明顯的相關性。建議採用循序漸進的上升方式來預防 HAPE。

Nifedipine 硝苯地平：硝苯地平是一種鈣離子阻斷劑，可促進血管擴張並降低肺動脈壓。應在上升前一天開始服用硝苯地平，並持續服用直至開始下降或在最高海拔停留 4 天，如果上升速度超過建議的上升速度，則可能需要持續服用長達 7 天（表 1）。

犀利士(他達拉非tadalafil)：對於已知易感且不適合服用硝苯地平的個體，他達拉非可用於預防高海拔肺水腫（HAPE）（表1）。

硝苯地平和他達拉非不宜同時使用。

(威而鋼相關研究比犀利士少. 不列為預防用藥建議)

預適應和分階段攀登：分階段攀登和預適應可能是預防HAPE的合理方法。然而，目前尚不確定達到預期效果所需的適度海拔暴露的強度和持續時間。

HAPE診斷

高海拔肺水腫 (HAPE) 的診斷需要非常特定的臨床背景——例如，未適應高原環境的低地居民攀登至海拔 ≥2500 公尺的高度——並依賴於一組特徵性症狀，包括活動性呼吸困難，且程度遠超以往在高海拔地區的經歷或同等高度下其他個體所經歷的呼吸困難。患者也可能出現乾咳、疲倦、虛弱和胸悶。隨著病情進展，患者在輕微活動或休息時即出現呼吸困難，並可能出現紫紺和咳出粉紅色泡沫痰。

如果條件允許，脈搏血氧飽和度監測可以確認是否存在與預期海拔高度不符的低氧血症。然而，在高海拔地區使用指尖血氧儀時必須格外謹慎，因為在高海拔地區，氧飽和度會隨著氧分壓的微小變化而迅速改變，且當動脈血氧飽和度低於 80% 時，儀器的準確性會下降。

在特定海拔高度下，正常的血氧飽和度可能無法精確地確定，應將其視為一個數值範圍，而非一個具體數值。因此，臨床決策不應基於一段時間內或個體間血氧飽和度的微小差異。

此外，應盡量減少導致測量誤差的因素，例如四肢冰冷、環境光線過強、血氧儀探頭不合適等。

也應考慮其他在高海拔地區引起呼吸道症狀的原因，例如氣喘、支氣管痙攣、肺炎、氣胸、肺栓塞、病毒性上呼吸道感染、心臟衰竭或心肌梗塞。高海拔肺水腫

高海拔肺水腫的治療

建議：如果懷疑或確診為HAPE，應在條件允許的情況下開始吸氧，並開始下降至較低海拔。如果下降不可行或延遲，則應繼續吸氧，或將患者置於便攜式高壓氧艙內。

發生高海拔肺水腫（HAPE）的患者，只有在HAPE症狀完全消退，且在休息和輕度運動時，無需吸氧和/或使用血管擴張劑治療，並能維持穩定的氧合狀態後，才能考慮進一步攀登更高海拔或再次攀登。

下降：

與AMS和HACE一樣，下降仍然是治療HAPE的最佳方法。

患者應嘗試下降至少1000米，或直至症狀消退。

下降過程中應盡可能減少體力消耗（例如，不攜帶背包或搭乘機動車、直升機或動物運輸），因為體力消耗會進一步增加肺動脈壓，加重水腫。

吸氧：

如有條件，在等待開始下降、無法下降以及重症患者下降過程中，應使用足夠的氧氣，使血氧飽和度（SpO2）達到90%以上或緩解症狀。

攜帶式高壓氧艙：

與急性高山症（AMS）和高海拔腦水腫（HACE）類似，當下撤不可行或延遲，或無法取得補充氧氣時，便攜式高壓氧艙可用於治療高海拔肺水腫（HAPE）。

硝苯地平(Nifedipine 鈣離子阻斷劑. 降血壓藥物)

當下撤不可能或延遲，且無法可靠地獲得補充氧氣或便攜式高壓氧治療時，應使用硝苯地平治療高海拔肺水腫（表1）。

磷酸二酯酶抑制劑：(犀利士; 威而鋼)

由於磷酸二酯酶抑制劑能夠擴張肺血管並降低肺動脈壓，因此在治療高海拔肺水腫方面具有充分的生理依據。因此，當下撤不可能或延遲，無法獲得補充氧氣或便攜式高壓氧治療，且無法使用硝苯地平時，可使用他達拉非或西地那非治療高海拔肺水腫。

(萬不得已才用威而鋼或犀利士治療 HAPE)

(在2024WMS更新的藥物表格並未將犀利士或威而鋼列入HAPE治療)

持續性呼吸道正壓通氣（CPAP）：

正壓通氣透過增加肺泡壁的跨壁壓來發揮作用，從而增加肺泡容積並改善氣體交換。當無法使用補充氧氣或肺血管擴張劑治療高海拔肺水腫（HAPE）時，或作為對單獨使用補充氧氣無反應的患者的輔助治療，可考慮使用CPAP。

合併HAPE和高海拔腦水腫（HACE）的患者：

對於合併神經功能障礙且在給予補充氧氣和氧飽和度改善後仍未迅速緩解的HAPE患者，應在治療方案中加入地塞米松，劑量與HACE的劑量相同（表1）。合併HAPE和HACE的患者，可使用硝苯地平或其他肺血管擴張劑，但需注意避免降低全身血壓。

圖1. 評估AAI風險。

Figure 1. Assessing the risk of acute altitude illness. 

病史和計​​畫攀登的特徵可用於評估攀登後發生急性高原病的風險。請在最能描述左側列中各項變數的方格內打勾。計劃攀登的風險由最右側打勾的列決定。此評估適用於未適應高原環境的人員。假設攀登從海拔低於 1200 公尺的海拔開始。先前急性高原病史並不一定意味著未來所有攀登都存在高風險，因為在後續行程中降低攀登速度或目標海拔可能有助於避免問題。透過確保適當緩慢的攀登速度，可以降低在任何給定海拔以上旅行的風險。既往急性高原病的嚴重程度可使用表 2 的資訊進行分級。

 AMS，急性高原病；HACE，高原腦水腫；HAPE，高原肺水腫。

表1. 預防及治療高海拔疾病的藥物建議劑量
1. 對於攀登至並停留於特定海拔高度的人員，到達目標海拔高度後，若遵循建議的攀登速度，則應繼續用藥2天；若攀登速度超過建議速度，則應繼續用藥2-4天。若攀登至目標海拔高度後立即下降，則可在開始下降後停止用藥。
2. 此劑量適用於低至中度風險的攀登情況。對於高風險的攀登情況，可考慮每日兩次，每次250毫克。海拔5000公尺以上的攀登，合適的劑量尚不清楚。 
3. 乙醯唑胺也可作為地塞米鬆的輔助藥物用於高山腦水腫的治療，但地塞米松仍是高山腦水腫的主要治療藥物。


4. 對於需要進行高原肺水腫預防的人員，若攀登至目標海拔並停留在該海拔，則在到達目標海拔後，若遵循建議的攀登速度，應繼續用藥4天；若攀登速度超過建議速度，則應繼續用藥4-7天。若攀登至目標海拔高度後立即下撤，則可在下撤開始後停止用藥。

表2. AMS分類

Introduction
Travel to elevations above 2500 m is associated with risk of developing one or more forms of acute altitude illness: acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). Although unacclimatized individuals are at risk of high altitude illness when ascending to altitudes above 2500 m, it is possible to see acute altitude illness present at lower elevations due to a high degree of variability in responses to high altitude between individuals.

To provide guidance to clinicians and disseminate knowledge about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention, diagnosis, and treatment of acute altitude illness. Preventive and therapeutic modalities are presented, and recommendations made for each form of acute altitude illness.

Acute Mountain Sickness and High Altitude Cerebral Edema
From a clinical standpoint, HACE represents an extremely severe form of AMS; therefore, preventive and treatment measures for the two disorders can be addressed simultaneously.

AMS/HACE Prevention
Suggested Approach: The approach to prevention of AMS and HACE should be a function of the risk profile of the individual traveling to high altitude (Figure 1). The first priority should be ensuring gradual ascent to the target elevation. Travelers can lower their risk by sleeping one night at an intermediate altitude. For example, sea level residents traveling to Colorado resort areas over 2800 m can spend one night in Denver (1600 m). If travelers are unable to ascend gradually due to various logistical factors, pharmacologic prophylaxis can be considered. Prophylactic medications are generally not necessary in low risk situations but should be considered in addition to gradual ascent for use in moderate to high risk situations (Figure 1). With travel above 3000 m, individuals should not increase the sleeping elevation by more than 500 m per day and should include a rest day (i.e. no ascent to higher sleeping elevation) every 3-4 days.

Acetazolamide: 

Acetazolamide has an established role in prevention of AMS. There is a risk, albeit extremely low, of inciting an allergic reaction in persons with sulfonamide allergy when taking acetazolamide, and the drug is contraindicated in persons with any prior anaphylactic reaction to a sulfonamide medication or a history of Stevens-Johnson syndrome. Acetazolamide should be started the day before ascent but will still have beneficial effects if started on the day of ascent (Table 1).


Dexamethasone: 

Dexamethasone does not facilitate acclimatization like acetazolamide but has an established benefit in AMS prevention. Higher doses than those recommended in Table 1 (4 mg every 6 hours) may be considered only in very high risk situations such as military or search and rescue personnel being airlifted to altitudes > 3500 m with immediate performance of physical activity. If used for longer than 5-7 days, dexamethasone should be tapered over a one week period rather than stopped abruptly. It is not recommended for AMS prevention in children. Dexamethasone should be started the day before ascent but will still have beneficial effects if started on the day of ascent.


Ibuprofen: 

Ibuprofen cannot be recommended over acetazolamide or dexamethasone for AMS prevention during rapid ascent (Table 1), however, it could be used in persons who do not wish to take acetazolamide or dexamethasone or have allergies or intolerance to these medications.


Staged Ascent and Preacclimatization: 

The panel does not endorse a particular protocol for preacclimatization (i.e., repeated exposures to hypoxia preceding high altitude travel) and staged ascent (i.e., staying at a moderate elevation for several days before ascending to the target elevation) as a means of AMS prevention. With regard to normobaric hypoxia exposure in a hypoxic tent, only sufficiently long exposures (> 8 hours per day) that can be undertaken regularly over an appropriate number of weeks are likely to offer any significant preacclimatization benefit.


Other Options: 

The following interventions have not been shown to be of benefit: chewed coca leaves, coca tea and other coca-derived products; “forced” or “over” hydration; short-term oxygen use in the form of either visits to oxygen bars or over-the-counter oxygen delivery systems by which individuals inhale oxygen-enriched gas from a small pre-filled canister; other over-the-counter products, such as powdered drink mixes, patches, and oral supplements.

AMS/HACE Diagnosis
The diagnosis of AMS is made in a very specific clinical context, that of an unacclimatized lowlander who becomes ill within several hours to 3 days following ascent to high elevations, generally >2500 m. Diagnosis is based solely on reported symptoms, as there are no characteristic findings on physical exam or diagnostic laboratory studies. Symptoms of AMS include: headache, anorexia, nausea, fatigue, and light-headedness or dizziness. In line with the updated Lake Louise Acute Mountain Sickness Score (see Table 2), these guidelines emphasize the role of headache and de-emphasize the role of sleep disruption in the diagnosis of AMS. The best approach to diagnosis is to consider the traveler’s well-being and functional status. Individuals who feel ill and/or must reduce their daily activities several hours to 3 days following ascent to elevations >2500 m likely have AMS.

The diagnosis of HACE is heralded by signs of encephalopathy including ataxia–which is often the earliest clinical finding–and altered mentation. Other signs include apathy, irritability, lassitude, and inability to provide self-care, all of which can be subtle. Untreated HACE can progress to coma. Focal neurologic deficits are unusual and should prompt consideration of other diagnoses. Heel-to- toe walking can be used to gauge ataxia, and papilledema can confirm cerebral edema.

AMS/HACE Treatment
Suggested Approach: Care should be taken to exclude disorders whose symptoms and signs resemble those seen with AMS and HACE, such as cerebrovascular accident, carbon monoxide poisoning, hypoglycemia, hyponatremia, infection, or traumatic brain injury.
這張危險分級是用於預測高海拔疾病風險. 包含 AMS. HACE. HAPE
有些文獻的危險分級是用於預測 AMS 風險
兩種並不相同.



Persons with AMS of any severity or HACE should cease ascending and may need to consider descent, depending on the severity of illness and circumstances. Individuals with AMS may resume ascending once symptoms resolve. Further ascent or reascent to a previously attained altitude should never be undertaken if there are ongoing symptoms. Descent should be initiated in any suspected HACE victim or if symptoms of AMS are worsening despite treatment with acetazolamide or dexamethasone. Dexamethasone is considered to be a more reliable pharmacological treatment for moderate to severe AMS/HACE than acetazolamide. If descent is not feasible, supplemental oxygen or a portable hyperbaric chamber should also be used.

Supplemental Oxygen: 

Oxygen, if available, delivered by nasal cannula or mask at flow rates sufficient to relieve symptoms provides a suitable alternative to descent. It should also be used when descent is recommended but not feasible or during descent in severely ill individuals. An SpO2 > 90% is usually adequate. Short-term oxygen use in the form of over-the-counter oxygen canisters should not be relied on for this purpose.


Portable Hyperbaric Chambers: 攜帶型加壓艙/袋

Portable hyperbaric chambers are effective for treating severe altitude illness but require constant tending by care providers and are difficult to use with claustrophobic or vomiting patients. In many cases, ill individuals may improve enough that they can assist with their evacuation and descend once symptoms improve. Use of a portable hyperbaric chamber should not delay descent in situations where descent is required.

Acetazolamide: 丹木斯

Acetazolamide should be considered for treatment of AMS. (Table 1).

Dexamethasone: 類固醇

Dexamethasone is very effective for treating AMS. The medication does not facilitate acclimatization, so further ascent should be delayed until the patient is asymptomatic while off the medication. Extensive clinical experience supports using dexamethasone in patients with HACE (Table 1).

Medication	Indication	Route	Dosage
Acetazolamide	AMS, HACE Prevention	Oral	125 mg every 12 h 1, 2 Pediatrics: 1.25 mg•kg-1 every 12 h (maximum 125 mg per dose)
	AMS Treatment 3	Oral	250 mg every 12 h Pediatrics: 2.5 mg•kg-1 every 12 h (maximum: 250 mg per dose)
Dexamethasone	AMS, HACE Prevention	Oral	2 mg every 6 h or 4 mg every 12 h 1 Pediatrics: Should not be used for prophylaxis
	AMS, HACE Treatment	Oral, IV, IM	AMS: 4 mg every 6 h HACE: 8 mg once then 4 mg every 6 h Pediatrics: 0.15 mg•kg-1•dose-1 every 6 h (Maximum: 4 mg per dose)
Ibuprofen	HAH Treatment	Oral	600 mg every 8 h
Nifedipine	HAPE Prevention	Oral	30 mg ER version, every 12 h or 20 mg ER version every 8 h 4
	HAPE Treatment	Oral	30 mg ER version, every 12 h or 20 mg ER version every 8 h
Tadalafil	HAPE Prevention	Oral	10 mg every 12 h 4
Sildenafil	HAPE Prevention	Oral	50 mg every 8

High Altitude Pulmonary Edema

HAPE Prevention
Suggested Approach: 

Because the rates of acclimatization and physiologic responses to high altitude vary considerably among individuals, the ascent profile recommendations presented here do not guarantee HAPE prevention in all high altitude travelers. A gradual ascent profile is the primary method for preventing HAPE; the recommendations provided above for AMS and HACE prevention also apply to HAPE prevention. Pharmacologic prophylaxis should only be considered for individuals with a history of HAPE, especially multiple episodes.

Gradual Ascent: 

There is a clear relationship between rate of ascent and disease incidence. Gradual ascent is recommended to prevent HAPE.

Nifedipine: 

A calcium channel blocker that promotes vasodilation and lowers pulmonary artery pressure, nifedipine should be started the day prior to ascent and continued either until descent is initiated or the individual has spent 4 days at the highest elevation, perhaps up to 7 days if the individual ascended faster than recommended ascent rates (Table 1).

Tadalafil: 

Tadalafil can be used for HAPE prevention in known susceptible individuals who are not candidates for nifedipine (Table 1). There is no role for concurrent use of nifedipine and tadalafil.

Preacclimatization and Staged Ascent: 

Staged ascent and preacclimatization may offer a reasonable means of HAPE prevention. However, uncertainty remains as to the magnitude and duration of moderate altitude exposure necessary to yield benefit.

HAPE Diagnosis
The diagnosis of HAPE requires a very specific clinical context–an unacclimatized lowlander ascending to elevations ≥2500 m–and relies on a characteristic set of symptoms, including dyspnea on exertion out of proportion to previous experiences at high altitude or that experienced by other individuals at the same elevation. Nonproductive cough, fatigue, weakness, and gurgling sensation in the chest may also be present. With progression, individuals become dyspneic with mild exertion or at rest and may develop cyanosis and cough productive of pink frothy sputum. 

If available, pulse oximetry can confirm the presence of hypoxemia out of proportion to that expected for a given elevation, however, care must be exercised when using fingertip oximeters at high altitude, as oxygen saturation changes rapidly in response to small changes in oxygen tensions at high altitude and device accuracy declines with arterial oxygen saturations of less than 80%. The normal oxygen saturation at a given elevation may not be known with certainty and should be viewed as a range of values, rather than a specific number. For these reasons, clinical decisions should not be based on small differences in saturation over time or among individuals. Effort should also be made to minimize factors that cause measurement errors, including cold extremities, excess ambient light, and ill-fitting oximeter probes.

Consideration should be given to other causes of respiratory symptoms at high altitude, such as asthma, bronchospasm, pneumonia, pneumothorax, pulmonary embolism, viral upper respiratory tract infection, heart failure, or myocardial infarction.

HAPE Treatment
Suggested Approach: 

If HAPE is suspected or diagnosed, oxygen should be started, if available, and descent initiated to lower elevation. If descent is infeasible or delayed, supplemental oxygen should be continued, or the individual should be placed in a portable hyperbaric chamber. Individuals who develop HAPE may consider further ascent to higher altitude or reascent only when symptoms of HAPE have completely resolved and they maintain stable oxygenation at rest and with mild exercise while off supplemental oxygen and/or vasodilator therapy.

Descent: 

As with AMS and HACE, descent remains the single best treatment for HAPE. Individuals should try to descend at least 1000 m or until symptoms resolve. They should exert themselves as little as possible while descending (e.g. travel without a pack or via motor vehicle, helicopter or animal transportation) because exertion can further increase pulmonary artery pressure and exacerbate edema formation.

Supplemental Oxygen: 

When available, supplemental oxygen sufficient to achieve an SpO2 > 90% or relieve symptoms should be used while waiting to initiate descent, when descent is infeasible and during descent in severely ill patients.

Portable Hyperbaric Chambers: 

As for AMS and HACE, portable hyperbaric chambers can be used for HAPE treatment when descent is infeasible or delayed or supplemental oxygen is unavailable.

Nifedipine:

 Nifedipine should be used for HAPE treatment when descent is impossible or delayed and reliable access to supplemental oxygen or portable hyperbaric therapy is unavailable (Table 1).


Phosphodiesterase Inhibitors: 

By virtue of their ability to cause pulmonary vasodilation and decrease pulmonary artery pressure, there is a strong physiologic rationale for using phosphodiesterase inhibitors in HAPE treatment. Therefore, tadalafil or sildenafil can be used for HAPE treatment when descent is impossible or delayed, access to supplemental oxygen or portable hyperbaric therapy is impossible, and nifedipine is unavailable.

Continuous Positive Airway Pressure (CPAP):

Positive airway pressure works by increasing transmural pressure across alveolar walls, thereby increasing alveolar volume and subsequent gas exchange. CPAP may be considered for treatment of HAPE when supplemental oxygen or pulmonary vasodilators are not available or as adjunctive therapy in patients not responding to supplemental oxygen alone.

Patients with Concurrent HAPE and HACE
For HAPE patients with neurologic dysfunction that does not resolve rapidly with administration of supplemental oxygen and improvement in the patient’s oxygen saturation, dexamethasone should be added to the treatment regimen at the doses described for HACE (Table 1). Nifedipine or other pulmonary vasodilators may be used in patients with concurrent HAPE and HACE, with care to avoid lowering systemic blood pressure.

Figure 1. 

Assessing the risk of acute altitude illness. Medical history and features of the planned ascent can be used to assess the risk of acute altitude illness after ascent. Check marks should be placed in the boxes that best describe the variables in the left-hand column. The risk of a planned ascent is determined by the farthest column to the right in which a check mark is placed. This assessment applies to unacclimatized individuals. Ascent is assumed to start from elevations <1200 m. A history of acute altitude illness does not necessarily reflect high risk with all future ascents, as a slower ascent rate or lower target elevation on subsequent trips may help avoid problems. The risk of travel above any given elevation can be mitigated by ensuring an appropriately slow rate of ascent. The severity of prior AMS can be graded using the information in Table 2. AMS, acute mountain sickness; HACE, high altitude cerebral edema; HAPE, high altitude pulmonary edema.
Table 1. Recommended Dosages for Medications Used in the Prevention and Treatment of Altitude Illness

table 1 註解
AMS: Acute mountain sickness; ER: extended release; HACE: High altitude cerebral edema; HAH: High altitude headache; HAPE: High altitude pulmonary edema
1 For individuals ascending to and remaining at a given elevation, following arrival at the target elevation, the medication should be continued for 2 days in individuals adhering to the recommended ascent rate and 2-4 days in individuals ascending faster than recommended rates. Individuals who ascend to a target elevation and immediately descend can stop the medication once descent is initiated.
2 This dose applies to low-moderate risk ascent profiles. For high-risk ascent profiles, consider 250 mg BID. The appropriate dose for ascent above 5000 m is not clear.
3 Acetazolamide can also be used at this dose as an adjunct to dexamethasone in HACE treatment, but dexamethasone remains the primary treatment for HACE.
4 For individuals requiring HAPE prophylaxis, ascending to and remaining at a given elevation, following arrival at the target elevation, the medication should be continued for 4 days in individuals adhering to the recommended ascent rate and 4-7 days in individuals ascending faster than recommended rates. Individuals who ascend to a target elevation and immediately descend can stop the medication once descent is initiated.

Table 2. Acute Mountain Sickness Classification

Category	Mild AMS	Moderate-Severe AMS	High Altitude Cerebral Edema (HACE)
Symptoms	Headache plus one or more other symptoms (nausea/vomiting; fatigue, lassitude, dizziness).   All symptoms of mild intensity	Headache plus one or more other symptoms (nausea/vomiting; fatigue, lassitude, dizziness). All symptoms of moderate-severe intensity	Worsening of symptoms seen in moderate to severe AMS
Signs	None	None	Ataxia, severe lassitude, altered mental status, encephalopathy
Lake Louise AMS Score	3-5	6-12	Not applicable