野外與登山醫學-2025 CDC 高海拔旅遊與高海拔疾病 High-Altitude Travel and Altitude Illness

2026-01-22 10:53AM

統一名詞翻譯

Dexamethasone 類固醇(地塞米松), 高海拔疾病的研究或文獻. 提到的類固醇幾乎都是指 dexamethasone(類固醇種類很多,不僅地塞米松一種)
HAI= high altitude illness 高海拔疾病(等於高山症)
AMS =acute mountain sickness 急性高山病(不等於高山症)
HAC=E high altitude cerebral edema 高海拔腦水腫
HAPE =high altitude pulmonary edema 高海拔肺水腫
Acetazolamide 丹木斯(乙酰唑胺). 一種利尿劑
Nifedipine 硝苯地平, 是一種降血壓藥物, 分類上屬於鈣離子阻斷劑CCB, 於1969年被合成，1981年在美國核准上市。

這篇筆記是將CDC關於高海拔疾病全部內容貼上

High-Altitude Travel and Altitude Illness  高海拔旅行與高海拔疾病

熱門高海拔旅遊目的地包括科羅拉多州的滑雪勝地，例如

韋爾和布雷肯里奇，其住宿地點分別位於海拔2480公尺和2925公尺

（8150英尺和9600英尺）處。
秘魯庫斯科（海拔約3350公尺；11000英尺）
玻利維亞拉巴斯（海拔約3650公尺；12000英尺）
西藏自治區拉薩（海拔約3700公尺；12100英尺）
尼泊爾珠穆朗瑪峰大本營（約5,400公尺；17,700英尺）
坦尚尼亞乞力馬扎羅山（約5,900公尺；19,341英尺）

高海拔環境會使旅行者面臨寒冷、低濕度、紫外線輻射增強和氣壓降低等問題，所有這些都可能導致健康問題。然而，最大的隱患是缺氧，這是由於氧分壓（PO2）降低所致。例如，在海拔約3050公尺（約10,000英尺）處，吸入氧分壓僅為海平面的69%；急性暴露於此低氧環境可使動脈血氧飽和度降至88%至91%。

低氧壓力的程度和後果取決於海拔高度、上升速度和暴露時間；宿主的遺傳因素也可能起作用。睡眠期間低氧血症最為嚴重；白天前往高海拔地區，晚上則回到低海拔地區，對身體的壓力也小得多。由於在上升到高海拔地區時增加通氣量至關重要，肺功能受損的旅行者必須謹慎，所有旅行者都應避免服用呼吸抑制劑。

適應性
人體可以適應海拔約5200公尺（≤17000英尺）以下的輕度低氧環境，但這需要時間。對高海拔的適應過程會持續數週至數月，但對於旅行者而言，上升後最初3-5天的急性適應過程至關重要。急性期表現為通氣量持續增加、氧合改善、腦血流量的變化。紅血球生成增加在急性適應過程中並不起作用，儘管最初幾天血漿容量的減少確實會導致血紅蛋白濃度升高。
高海拔疾病可能在急性適應過程完成之前發生，但不會之後發生。除了預防高海拔疾病外，適應過程還能改善睡眠，提高舒適度和幸福感，並增強次最大強度耐力；在高海拔地區，最大運動表現總是會低於在低海拔地區。
旅行者可以透過調整行程來優化適應過程，避免「爬升過快過高」（見方框3.5.1）。逐步上升或分階段上升能為身體提供關鍵的適應時間。例如，在前往更高海拔之前，先在海拔約2450公尺至2750公尺（8000-9000英尺）處適應至少2-3晚，可以顯著降低AMS的風險。野外醫學協會建議避免在一天內上升到2750公尺（≥9000英尺）的睡眠海拔；一旦超過3000公尺（9800英尺），睡眠海拔的上升速度不應超過每晚500公尺（1650公尺）；並且每上升1000公尺（3300英尺）的睡眠海拔，就需要額外增加一晚的適應時間。這些合理的建議對某些旅行者來說可能太快，對另一些旅行者來說可能太慢。

Table 3.5.1

適應高海拔環境小秘訣：旅客須知清單
逐漸上升。

避免一天之內直接從低海拔（1200 公尺或 <4000 英尺）上升到 2750 公尺（>9000 英尺）的睡眠海拔。
一旦海拔超過 3,000 公尺（9,850 英尺），每天睡眠海拔的移動幅度不得超過 500 公尺（1,600 英尺），且每增加 1,000 公尺（3,300 英尺）的睡眠海拔，就需要額外安排一天的適應期。
如果不可避免地需要突然上升，可以考慮使用乙醯唑胺來加速適應海拔高度。
在高海拔地區的前48小時內避免飲酒。
如果經常攝取咖啡因，請繼續攝入，以避免戒斷性頭痛，這種頭痛可能會與AMS引起的頭痛混淆。
在高海拔地區的前 48 小時內，只能進行輕度運動。
在旅行前 14 天內，在高海拔地區（>2,750 公尺；>9,000 英尺）進行 2 晚或以上的適應性訓練是有益的，但越接近旅行出發日期越好。

高海拔疾病對旅行者的風險

對高原病的易感性和抵抗力部分取決於遺傳因素，但目前尚無簡便的篩檢測試可以預測風險。訓練和體能狀況並不影響風險。旅行者的性別對易感性的影響微乎其微，甚至沒有影響。兒童與成人一樣容易罹患高海拔疾病；50歲以上族群的風險略低。任何未適應高原環境的旅行者，如果前往海拔≥2450公尺（≥8000英尺）的睡眠地點——有時甚至更低——都面臨高原疾病的風險。此外，即使已經成功適應高原環境的旅行者，如果前往海拔更高的睡眠地點，尤其是在海拔升高600-900公尺（>2000-3000英尺）的情況下，也存在高原病的風險。

旅行者以往對高海拔的反應是未來旅行最可靠的參考指標，但前提是海拔高度和上升速度與上次相似，即便如此，這也不是萬無一失的預測方法。除了自我身體外，旅行者罹患高海拔疾病的風險還受另外兩個主要因素的影響：進入高海拔地區的海拔高度和隨後的上升速度（表3.5.1）。由於個體體質差異以及出發點和地形的不同，制定完全避免高海拔疾病的行程並非易事。旅行者的目標或許並非完全避免高海拔疾病的所有症狀，而是盡量減少症狀，避免行程變更或需要醫療協助或撤離。

表 3.5.1：AMS 發生的風險類別*

註記
*假設起始海拔低於1200公尺（4000英尺）

縮寫：HACE，高海拔腦水腫；HAPE，高海拔肺水腫；AMS，急性高山病。
表 3.5.1 各類別的建議如下：
低風險：無需使用乙醯唑胺預防。旅行者應攜帶非處方止痛藥以應對頭痛，並備有乙醯唑胺，以便在必要時加快適應高山症環境或治療早期急性高山症。

中度風險：乙醯唑胺預防可能有效；可考慮使用。建議旅客攜帶乙醯唑胺以預防或治療急性高山症，並考慮處方地塞米松以備緊急情況使用。
高風險：強烈建議服用乙醯唑胺預防，並建議旅客攜帶地塞米松以備緊急情況使用。

存在風險的目的地
一些常見的高海拔目的地需要搭乘飛機快速爬升至海拔超過 3400 公尺（11150 英尺）的高度，這使得旅客面臨較高的高山症風險。旅遊醫學中常見的問題是，當無法進行漸進式或分階段適應時，是否應該建議旅客服用乙醯唑胺。鑑於在這些情況下高山症的發生率接近 50%，建議降低藥物預防的閾值。在某些情況下（例如庫斯科和拉巴斯），旅客可以下降到低於機場海拔的地方休息 1-2 晚，然後再開始爬升，這樣或許可以避免服用藥物。

尼泊爾部分健行路線，尤其是珠峰大本營路線，行程安排會超出許多人的適應能力。即使按照標準的適應計畫進行，在高海拔地區，高山症的發生率也可能接近30%。因此，盡可能延長徒步行程，可以使旅程更加愉快和安全。

高海拔疾病HAI
HAI分為三種綜合症：急性高山病（AMS）、高海拔腦水腫（HACE）和高海拔肺水腫（HAPE）。一些醫療專業人員認為高山症是一種獨立的疾病，因為孤立性頭痛可能單獨發生，而沒有AMS的典型症狀。

急性高山症
急性高山症是最常見的高山症，例如，在科羅拉多州海拔超過 2450 公尺（8000 英尺）的地方過夜的遊客中，有 25% 的人會患上急性高山症。

診斷
AMS的診斷是基於近期高海拔攀登史和主觀症狀。 AMS 的症狀與宿醉類似；頭痛是主要症狀，通常伴隨以下至少一種症狀：厭食、頭暈、疲勞、噁心，或偶爾嘔吐。少數情況下，AMS 不會出現頭痛。症狀通常在抵達高海拔地區或攀登至更高海拔後 2-12 小時內出現，且常在第一晚或之後出現。尚不會說話的兒童患有 AMS 時可能出現食慾不振、易怒和臉色蒼白。如果旅行者不再繼續攀登，AMS 通常會在 12-48 小時內消退。




這種情況通常具有自限性，會在 1-3 天內出現並消退。抵達高海拔地區 3 天後出現症狀且未持續上升的，不應歸因於急性高山症 (AMS)。 AMS 沒有特徵性的徵兆；脈搏血氧飽和度通常在正常海拔範圍內或略低於正常值，而較高的動脈血氧飽和度 (SpO₂ )似乎對預防 AMS 有保護作用。由於脈搏血氧儀的價格低於 30 美元，旅行者可以隨身攜帶一個，以評估自身的適應情況。圖 3.5.1 顯示了 特定海拔高度下SpO₂的預期範圍。




急性高山症的鑑別診斷範圍很廣；常見的鑑別診斷包括酒精宿醉、一氧化碳中毒、脫水、藥物中毒、疲勞、低鈉血症和偏頭痛。與病毒感染不同，急性高山症不會出現流涕、發燒、畏寒或肌痛等症狀。患有急性高山症的旅客在下降≥300公尺（≥1000英尺）後症狀會迅速改善，這可以作為診斷急性高山症的有用指標。










筆記




縮寫：SpO2，氧飽和度；m，米。




換算：1,500 公尺 ≈ 4,900 英尺；2,500 公尺 ≈ 8,200 英尺；3,500 公尺 ≈ 11,500 英尺；4,500 公尺 ≈ 14,750 英尺；5,500 公尺 ≈ 1,8,000 英尺




治療




急性高山症（AMS）症狀通常在下降300公尺（1000英尺）或以上時迅速緩解，尤其是在活動量較小的情況下。如果停留在症狀出現的海拔高度，以每分鐘1-2公升的流量補充氧氣，大約30分鐘內即可緩解頭痛，並在數小時內緩解其他AMS症狀，但這種氧氣通常難以獲得。市面上常見的便攜式小型壓縮氧氣罐可提供短暫的緩解，但其氧氣含量過低（最多5公升），不足以持續改善症狀。患有AMS但未出現高海拔腦水腫（HACE）或高海拔肺水腫（HAPE）（下文將對此進行描述）的旅行者可以安全地停留在當前海拔高度，並使用非阿片類鎮痛藥（例如，每8小時服用600毫克布洛芬或500毫克對乙酰氨基酚）和止吐藥（例如，4毫克昂丹司）進行自我治療。




乙醯唑胺能加速高山症適應並緩解急性高山症，但更常用於預防，療效也更可靠。地塞米鬆在快速緩解中重度急性高山症症狀方面比乙醯唑胺更有效。如果旅行者在相同海拔且經治療後症狀加重，則必須下降。




高原腦水腫

作為一種腦病，高海拔腦水腫（HACE）被認為是急性高山症的「末期」。幸運的是，HACE 較為罕見，尤其是在海拔低於 4,300 公尺（14,000 英尺）的地區。 HACE 通常是高海拔肺水腫（HAPE）引起的嚴重低氧血症的繼發性後果。




診斷




與急性精神狀態改變（AMS）不同，高酒精性腦水腫（HACE）主要表現為神經系統症狀，尤其是精神狀態改變、共濟失調、意識模糊和嗜睡，與酒精中毒相似。局部神經系統徵兆和癲癇發作在HACE中較為罕見；若出現這些症狀，應考慮顱內病變、癲癇或低鈉血症。其他鑑別診斷包括一氧化碳中毒、藥物中毒、低血糖、體溫過低和中風。發病後24小時內即可出現昏迷。




治療




在醫療資源豐富的地區，高海拔腦水腫（HACE）可使用吸氧和地塞米松治療。在偏遠地區，對於任何疑似患有HACE的患者，應立即啟動下撤程序，並儘可能同時給予地塞米松和氧氣。若下撤不可行，除地塞米松外，吸氧或使用攜帶式高壓氧艙可挽救生命。若不進行治療或下撤，患者很可能在共濟失調症狀後12-24小時內陷入昏迷。




高山肺水腫

HAPE 可單獨發生，也可與 AMS 和 HACE 同時發生；在科羅拉多州，其發病率約為每 10,000 名滑雪者中有 1 例，在海拔 >4,300 公尺（>14,000 英尺）的地區，其發病率 ≤每 100 名旅行者中有 1 例。




診斷




早期診斷至關重要；高海拔肺水腫（HAPE）的致死速度可能比高海拔腦水腫（HACE）更快。初期症狀包括胸悶、咳嗽、活動後呼吸困難加劇、運動能力下降。如果未能及時辨識和治療，HAPE 會發展為靜止呼吸困難和明顯的呼吸窘迫，常伴隨血痰。這種典型的 1-2 天進展過程很容易被識別為 HAPE，但對於通氣反應差的患者，病情可能僅表現為中樞神經系統功能障礙，伴隨意識混亂和嗜睡，同時血氧飽和度（SpO2 ） 也相當低。




大多數患者都能聞到囉音。脈搏血氧飽和度監測有助於診斷；氧飽和度通常在 50% 至 70% 之間，比同海拔健康人群的氧飽和度低至少 10 個百分點。高原肺水腫的鑑別診斷包括支氣管痙攣、心肌梗塞、心臟衰竭、肺炎和肺栓塞。




治療




大多數情況下，下降是緊急且必須的。如有條件，應給予氧氣，並儘可能減少患者的活動。如果無法立即下降，則使用輔助氧氣或便攜式高壓氧艙至關重要。




對於輕度高海拔肺水腫（HAPE）患者，如果能夠獲得氧氣（例如在醫院或高海拔醫療診所），可能無需下降到較低海拔，只需在當前海拔接受2-4天的吸氧治療並臥床休息即可。在資源有限且容錯率較低的野外環境中，硝苯地平可作為下降、吸氧或可攜式高壓氧療法的輔助用藥。如果無法獲得硝苯地平，可以使用選擇性磷酸二酯酶抑制劑，但不建議同時使用多種肺血管擴張劑。下降和吸氧氣的治療效果遠優於藥物治療。




高海拔睡眠障礙

睡眠障礙是前往高海拔地區的旅客最常見的抱怨。雖然不一定與高山症有關，但它確實令人煩惱。在海拔約2700公尺（9000英尺）以上，一定程度的週期性呼吸幾乎普遍存在，並可能幹擾睡眠。此外，睡眠階段也會改變，覺醒次數也會增加。睡眠通常會隨著適應而改善，但並非總是如此。乙醯唑胺對週期性呼吸有效，並且由於它能提高夜間血氧飽和度（SpO2 ），因此也有助於改善其他睡眠障礙。不應使用酒精和阿片類藥物等呼吸抑制劑來幫助在高海拔地區入睡。半衰期較短的催眠藥，例如5毫克唑吡坦或5毫克紮來普隆，通常被認為安全有效，但服用後至少應等待8小時，待藥效消退後再進行其他活動。其他藥物如苯海拉明和褪黑素尚未進行研究，但它們不會抑制低氧通氣反應，小劑量使用被認為是安全的。
















乙醯唑胺

作用機制

預防性服用乙醯唑胺可加速人體對高海拔低氧環境的適應，進而降低急性高山症的發生率和嚴重程度。症狀出現後服用乙醯唑胺也能促進復原。此藥主要透過誘導碳酸氫鹽利尿和代謝性酸中毒發揮作用，從而抵消呼吸性鹼中毒，進而刺激通氣，增加肺泡和動脈氧合，尤其是在睡眠期間。服用乙醯唑胺後，通常需要3-5天才能完成的高海拔通氣適應只需一天即可完成。




劑量

預防性用藥的有效劑量為每12小時服用125毫克，可最大程度減少常見的副作用，例如感覺異常。從登山前一天開始服用，持續到到達高海拔地區的頭兩天；如果繼續攀登，則需延長用藥時間。乙醯唑胺也可根據急性高山症的症狀，在需要時間間歇性服用。迄今為止，唯一研究過的治療劑量是250毫克（間隔8小時服用兩次），儘管用於預防的較低劑量也取得了一定的療效。兒童用藥劑量為每日2.5至5毫克/公斤體重，分次服用，每次最多125毫克，每日兩次。




不良反應和過敏反應

對乙醯唑胺的過敏反應並不常見。乙醯唑胺是一種磺胺類衍生物，但尚未有抗菌磺胺類藥物與非抗菌磺胺類藥物之間存在交叉過敏反應的報告。因此，對磺胺類抗生素過敏的人可以服用乙醯唑胺。然而，有藥物過敏史或多種藥物過敏史者應謹慎使用。雖然乙醯唑胺本身並非不良反應，但它會抑制碳酸酐酶的活性。碳酸酐酶通常在飲用碳酸飲料時會催化舌頭上二氧化碳的分解。這會導致患者在舌頭上嚐到二氧化碳的味道，從而改變飲料的味道。




地塞米松

地塞米松可有效預防和治療急性高山症（AMS）和高海拔腦水腫（HACE），也可能預防高海拔肺水腫（HAPE）。與乙醯唑胺不同，如果在適應高海拔環境前停用地塞米松，可能會出現輕微的反彈。乙醯唑胺是預防登山過程中急性高山症的首選藥物，而地塞米松通常應保留用於治療，通常作為下撤過程中的輔助用藥。成人劑量為每6小時4毫克；很少需要服用超過1-2天。目前，在攀登高峰（例如阿空加瓜山和乞力馬扎羅山）的“登頂日”，使用地塞米松預防突發性高山症的趨勢日益增長。




布洛芬

近期研究表明，每8小時服用600毫克布洛芬有助於預防急性高山症，但效果不如乙醯唑胺。布洛芬無需處方即可購買，價格低廉，且耐受性良好。




硝苯地平

硝苯地平既能預防也能緩解高山肺水腫。預防方面，硝苯地平通常用於易感人群。成人預防或治療劑量為每12小時服用30毫克緩釋片，或每8小時服用20毫克。兒童服用硝苯地平劑量難以控制，體重低於50公斤的兒童通常優選氨氯地平。




磷酸二酯酶-5抑制劑

磷酸二酯酶-5抑制劑可選擇性降低肺動脈壓，對全身血壓的影響小於硝苯地平。在登山過程中，每日兩次服用10毫克他達拉非可預防高山肺水腫。目前，他也在研究其作為潛在治療方法的潛力。




預防嚴重的高原病或死亡

向旅客解釋高山症的主要目的並非消除輕微高山症的可能性，而是預防重症、需要撤離甚至死亡。由於高山症的症狀出現和臨床過程都比較緩慢且可預測，除非因天氣或地理位置等原因被困在無法下降且無法獲得治療的情況下，否則沒有人會死於高山症。旅行者可以遵循以下三條規則來幫助預防高山症導致的死亡或嚴重後果：




了解高山症的早期症狀（與宿醉類似），並願意在出現症狀時予以重視。

即使症狀看起來再輕微，出現高山症症狀時也絕對不要在高海拔地區睡覺。

如果在原海拔高度休息或治療後症狀仍加重，則應下降海拔。

對於前往偏遠高海拔地區的健行團和探險隊來說，由於下降到較低海拔可能存在困難，加壓袋（例如 Gamow 袋）會很有幫助。腳踏式氣泵可增加 0.14 kg/cm²（2 lb/in²）的氣壓， 模擬下降約 1500-1800 公尺（5000-6000 英尺）的海拔高度，具體下降高度取決於起始海拔。加壓袋和氣泵的總重量約為 6.5 kg（14 磅）。




既往病史

患有既往疾病的旅客 必須在出發前優化治療方案，確保病情穩定。此外，這些旅客應制定應對高原疾病加重的方案。患有潛在疾病（例如冠狀動脈疾病、任何形式的慢性肺病或既往低氧血症、阻塞性睡眠呼吸中止症[OSA]或鐮狀細胞性狀）的旅客，即使病情控制良好，也應在出行前諮詢熟悉高原醫學問題的醫生（表3.5.3）。




為旅行者提供建議的醫護人員應該了解，在大多數高海拔度假勝地和城市，家用氧氣很容易獲得，但在美國則需要處方。根據具體情況，補充氧氣（無論是持續吸氧、間歇吸氧還是夜間吸氧）都能非常有效地將氧合恢復到低海拔水平，並消除高山症和原有疾病惡化的風險。
















糖尿病

糖尿病患者可以安全前往高海拔地區旅行，但如果參加劇烈運動，則必須習慣運動，並應密切監測血糖。高山症可能誘發糖尿病酮酸中毒，服用乙醯唑胺的患者治療較為困難。並非所有血糖儀在高海拔地區都能準確讀數。




阻塞性睡眠呼吸中止症

患有睡眠呼吸障礙且計劃進行高海拔旅行的旅客應服用乙醯唑胺。輕度至中度阻塞性睡眠呼吸中止症（OSA）患者，如果在家中沒有缺氧，可能無需使用持續性正壓呼吸器（CPAP）設備；而重度OSA患者則應避免高海拔旅行，除非他們在CPAP治療的基礎上額外吸氧。在無法使用電源的情況下，口腔矯正器可以作為OSA的有效輔助。




懷孕

目前尚無研究或病例報告描述孕婦在懷孕期間短暫前往高海拔地區會對胎兒造成傷害。然而，醫護人員建議孕婦不要在海拔超過3050公尺（10000英尺）的地方過夜，這或許是明智之舉。懷孕期間前往高海拔地區旅行前，必須確認孕婦健康狀況良好，且懷孕風險較低。應告知孕婦在偏遠山區旅行可能面臨的妊娠併發症風險。




放射狀角膜切開術

大多數人在高海拔地區不會有視力問題。然而，在高海拔地區，一些接受過放射狀角膜切開術的人可能會出現急性遠視，甚至無法自理。雷射輔助原位角膜磨鑲術（LASIK）和其他一些較新的手術在高海拔地區可能只會引起輕微的視力障礙。

Introduction
Popular high-altitude travel destinations include
Colorado ski resorts such as Vail and Breckenridge, with lodgings at 2,480 and 2,925 m (8,150 and 9,600 ft), respectively
Cusco, Peru (approximately 3,350 m; 11,000 ft)
La Paz, Bolivia (approximately 3,650 m; 12,000 ft)
Lhasa, Tibet Autonomous Region (approximately 3,700 m; 12,100 ft)
Everest base camp, Nepal (approximately 5,400 m; 17,700 ft)
Mount Kilimanjaro, Tanzania (approximately 5,900 m; 19,341 ft)

High-altitude environments expose travelers to cold, low humidity, increased ultraviolet radiation, and decreased air pressure, all of which can cause health problems. The biggest concern, however, is hypoxia, due to the decreased partial pressure of oxygen (PO2). At around 3,050 m (approximately 10,000 ft), for example, the inspired PO2 is only 69% of that at sea level; acute exposure to this reduced PO2 can lower arterial oxygen saturation to 88–91%.

The magnitude and consequences of hypoxic stress depend on the altitude, rate of ascent, and duration of exposure; host genetic factors may also contribute. Hypoxemia is greatest during sleep; day trips to high-altitude destinations with an evening return to a lower altitude are much less stressful on the body. Because of the key role of increased ventilation on ascent to high altitudes, travelers with compromised lung function must be cautious, and all travelers should avoid taking respiratory depressants.

Acclimatization
The human body can adjust to moderate hypoxia at altitudes up to approximately 5,200 m (≤17,000 ft) but requires time to do so. Some acclimatization to high altitude continues for weeks to months, but the acute process, which occurs over the first 3–5 days following ascent, is crucial for travelers. The acute phase is associated with a steady increase in ventilation, improved oxygenation, and changes in cerebral blood flow. Increased red cell production does not play a role in acute acclimatization, although a decrease in plasma volume over the first few days does increase hemoglobin concentration.

Altitude illness can develop before the acute acclimatization process is complete, but not afterward. In addition to preventing altitude illness, acclimatization improves sleep, increases comfort and sense of well-being, and improves submaximal endurance; maximal exercise performance at high altitude will always be reduced compared to that at low altitude.

Travelers can optimize acclimatization by adjusting their itineraries to avoid going "too high too fast" (Box 3.5.1). Gradually ascending to altitude or staging the ascent provides crucial time for the body to adjust. For example, acclimatizing for a minimum of 2–3 nights at around 2,450 to approximately 2,750 m (8,000–9,000 ft) before proceeding to a higher altitude is markedly protective against acute mountain sickness (AMS). The Wilderness Medical Society recommends avoiding ascent to a sleeping altitude of 2,750 m (≥9,000 ft) in a single day; ascending at a rate of no greater than 500 m (1,650 ft) per night in sleeping altitude once above 3,000 m (9,800 ft); and allowing an extra night to acclimatize for every 1,000 m (3,300 ft) of sleeping altitude gain. These reasonable recommendations can still be too fast for some travelers and too slow for others.

Box 3.5.1 Acclimatization tips: A checklist for travelers
1. Ascend gradually.

2. Avoid going directly from low altitude (1,200 m or <4,000 ft) to 2,750 m (>9,000 ft) sleeping altitude in one day.

3. Once above 3,000 m (9,850 ft), move sleeping altitude by no more than 500 m (1,600 ft) per day and plan an extra day of acclimatization for every additional 1,000 m (3,300 ft) of sleeping altitude gain. 

4. Consider using acetazolamide to speed acclimatization if abrupt ascent is unavoidable.
5. Avoid alcohol for the first 48 hours at high altitude.
6. If a regular caffeine user, continue using to avoid a withdrawal headache that could be confused with an altitude headache.
7. Participate in only mild exercise for the first 48 hours at altitude.
8. A high-altitude exposure (>2,750 m; >9,000 ft) for ≥2 nights, within 14 days before the trip, is useful but closer to the trip departure is better.

Altitude illness
Risk to travelers
Susceptibility and resistance to altitude illness are, in part, genetically determined traits, but there are no simple screening tests to predict risk. Training and physical fitness do not affect risk. A traveler's sex plays a minimal role, if any, in determining predisposition. Children are as susceptible as adults; people aged >50 years have slightly less risk. Any unacclimatized traveler proceeding to a sleeping altitude of ≥2,450 m (≥8,000 ft)—and sometimes lower—is at risk for altitude illness. In addition, travelers who have successfully adjusted to an altitude are at risk when moving to higher sleeping altitudes, especially if the altitude gain is 600–900 m (>2,000–3,000 ft).

How a traveler previously responded to high altitude is the most reliable guide for future trips but only if the altitude and rate of ascent are similar, and even then, this is not an infallible predictor. In addition to inherent susceptibilities, a traveler's risk for developing altitude illness is influenced by 2 other main factors: altitude of entry to high altitude and the subsequent rate of ascent (Table 3.5.1). Creating an itinerary to avoid any occurrence of altitude illness is difficult because of variations in individual susceptibility as well as in starting points and terrain. The goal for the traveler might not be to avoid all symptoms of altitude illness but to have no more than mild illness, thereby avoiding itinerary changes or the need for medical assistance or evacuation.

Table 3.5.1: Risk categories for developing acute mountain sickness (AMS)*

Notes
*Assumes starting altitude <1,200 m (<4,000 ft)Abbreviations: HACE, high-altitude cerebral edema; HAPE, high-altitude pulmonary edema; AMS, acute mountain sickness.

Recommendations for each category in Table 3.5.1 are as follows:

Low risk: Acetazolamide prophylaxis is not indicated. The traveler should carry over-the-counter analgesics for headache and have acetazolamide to speed acclimatization as necessary or to treat early AMS.
Medium risk: Acetazolamide prophylaxis would be beneficial; consider its use. Have the traveler carry acetazolamide for prevention or treatment of AMS and consider prescribing dexamethasone for emergency use.
High risk: Strongly encourage acetazolamide prophylaxis, and have the traveler carry dexamethasone for emergency use.

Destinations with risk
Some common high-altitude destinations require rapid ascent by airplane to >11,150 ft (>3,400 m), placing travelers in a high-risk category for AMS. A common travel medicine question is whether to recommend acetazolamide for travelers when gradual or staged acclimatization is not feasible. With rates of altitude illness approaching 50% in these situations, a low threshold for chemoprophylaxis is advised. In some cases (e.g., Cusco and La Paz), travelers can descend to elevations lower than the airport to sleep for 1–2 nights and then begin their ascent, perhaps obviating the need for medication.

Itineraries along some trekking routes in Nepal, particularly Everest base camp, push the limits of many people's ability to acclimatize. Even on standard acclimatization schedules, the prevalence of altitude illness can approach 30% at higher elevations. Whenever possible, adding extra days to the trek can make for a more enjoyable and safer trip.

Altitude illness syndromes
Altitude illness is divided into three syndromes: AMS; high-altitude cerebral edema (HACE); and high-altitude pulmonary edema (HAPE). Some healthcare professionals consider high-altitude headache a separate entity because isolated headache can occur without the combined symptoms that define AMS.

Acute mountain sickness
AMS is the most common form of altitude illness, affecting, for example, 25% of all visitors sleeping at altitudes >2,450 m (>8,000 ft) in Colorado.

Diagnosis
Diagnosis of AMS is based on a history of recent ascent to high altitude and the presence of subjective symptoms. AMS symptoms are like those of an alcohol hangover; headache is the cardinal symptom, usually accompanied by ≥1 of the following: anorexia, dizziness, fatigue, nausea, or, occasionally, vomiting. Uncommonly, AMS presents without headache. Symptom onset is usually 2–12 hours after initial arrival at a high altitude or after ascent to a higher elevation and often during or after the first night. Preverbal children with AMS can develop loss of appetite, irritability, and pallor. AMS generally resolves within 12–48 hours if travelers do not ascend farther.

The condition is typically self-limited, developing and resolving over 1–3 days. Symptoms starting after 3 days of arrival at high altitude and without further ascent should not be attributed to AMS. AMS has no characteristic physical findings; pulse oximetry is usually within the normal range for the altitude or slightly lower than normal, while a high arterial oxygen saturation (SpO2) for the altitude seems to be protective of AMS. With pulse oximeters available for under $30, travelers may want to have a pulse oximeter with them to gauge their acclimatization progress. Figure 3.5.1 shows the expected range of SpO2 for a given altitude.

The differential diagnosis of AMS is broad; common considerations include alcohol hangover, carbon monoxide poisoning, dehydration, drug intoxication, exhaustion, hyponatremia, and migraine. Unlike viral syndromes, there is no coryza, fever, chills, or myalgia. Travelers with AMS will improve rapidly with descent ≥300 m (≥1,000 ft), and this can be a useful indication for a diagnosis of AMS.

Notes
Abbreviations: SpO2, oxygen saturation; m, meters.
Conversions: 1,500 m = ~4,900 ft; 2,500 m = ~8,200 ft; 3,500 m = ~11,500 ft; 4,500 m = ~14,750 ft; 5,500 m = ~18,000 ft

Treatment
AMS improves rapidly with a descent of 300 m (1,000 ft) or more, especially if exertion is minimal. If staying at the altitude of onset, supplemental oxygen at 1–2 L per minute will improve headache within about 30 minutes and resolve other AMS symptoms over hours, although it is rarely available. The popular small, handheld cans of compressed oxygen can provide brief relief but contain too little oxygen (5 L at most) for sustained improvement. Travelers with AMS but without HACE or HAPE (both described below) can remain safely at their current altitude and self-treat with non-opiate analgesics (e.g., ibuprofen 600 mg or acetaminophen 500 mg every 8 hours) and antiemetics (e.g., ondansetron 4 mg orally disintegrating tablets).

Acetazolamide speeds acclimatization and resolves AMS but is more commonly used and better validated for use as prophylaxis. Dexamethasone is more effective than acetazolamide at rapidly relieving the symptoms of moderate to severe AMS. If symptoms worsen while the traveler is at the same altitude and despite treatment, descent is mandatory.

High-altitude cerebral edema
As an encephalopathy, HACE is considered "end-stage" AMS. Fortunately, HACE is rare, especially at elevations <4,300 m (<14,000 ft). HACE is often a secondary consequence of the severe hypoxemia that occurs with HAPE.

Diagnosis
Unlike AMS, HACE presents with neurological findings, particularly altered mental status, ataxia, confusion, and drowsiness, similar to alcohol intoxication. Focal neurologic findings and seizures are rare in HACE; their presence should lead to suspicion of an intracranial lesion, a seizure disorder, or hyponatremia. Other considerations for the differential diagnosis include carbon monoxide poisoning, drug intoxication, hypoglycemia, hypothermia, and stroke. Coma can ensue within 24 hours of onset.

Treatment
In populated areas with access to medical care, HACE can be treated with supplemental oxygen and dexamethasone. In remote areas, initiate descent for anyone suspected of having HACE, in conjunction with dexamethasone and oxygen, if available. If descent is not feasible, supplemental oxygen or a portable hyperbaric device, in addition to dexamethasone, can be lifesaving. Coma is likely to ensue within 12–24 hours of the onset of ataxia in the absence of treatment or descent.

High-altitude pulmonary edema
HAPE can occur by itself or in conjunction with AMS and HACE; incidence is roughly 1 per 10,000 skiers in Colorado, and ≤1 per 100 travelers at >4,300 m (>14,000 ft).

Diagnosis
Early diagnosis is key; HAPE can be more rapidly fatal than HACE. Initial symptoms include chest congestion, cough, exaggerated dyspnea on exertion, and decreased exercise performance. If unrecognized and untreated, HAPE progresses to dyspnea at rest and frank respiratory distress, often with bloody sputum. This typical progression over 1–2 days is easily recognizable as HAPE, but the condition in those with poor ventilatory response may present only as central nervous system dysfunction, with confusion and drowsiness, while SpO2 is quite low.

Rales are detectable in most victims. Pulse oximetry can aid in making the diagnosis; oxygen saturation values of 50–70% are common, which are at least 10 points lower than in healthy people at the same altitude. The differential diagnosis for HAPE includes bronchospasm, myocardial infarction, heart failure, pneumonia, and pulmonary embolism.

Treatment
In most circumstances, descent is urgent and mandatory. Administer oxygen, if available, and exert the patient as little as possible. If immediate descent is not an option, the use of supplemental oxygen or a portable hyperbaric chamber is critical.

Patients with mild HAPE who have access to oxygen (e.g., at a hospital or high-altitude medical clinic) might not need to descend to a lower altitude and can be treated with oxygen over 2–4 days and bedrest at the current altitude. In field settings, where resources are limited and the margin for error is lower, nifedipine can be used as an adjunct to descent, oxygen, or portable hyperbaric oxygen therapy. A selective phosphodiesterase inhibitor can be used if nifedipine is not available, but concurrent use of multiple pulmonary vasodilators is not recommended. Descent and oxygen are much more effective treatments than medication.

Sleep disturbance at high altitude
Sleep disturbance is the most common complaint of travelers to high altitudes. Although not necessarily associated with altitude illness, it can be bothersome. Above approximately 2,700 m (9,000 ft), some degree of periodic breathing becomes nearly universal and can interrupt sleep. In addition, sleep stage is altered and awakenings are frequent. Sleep generally but not always improves with acclimatization. Acetazolamide is effective for periodic breathing, and since it raises nocturnal SpO2, it can help with other aspects of altered sleep. Respiratory depressants such as alcohol and opiates should not be used to aid sleep at high altitude. Short half-life hypnotics, such as zolpidem 5 mg or zaleplon 5 mg, are recognized as generally safe and effective, but at least 8 hours after ingestion should be allowed for dissipation of effects before undertaking activities. Other agents such as diphenhydramine and melatonin have not been studied, but they do not depress the hypoxic ventilatory response and in small doses are considered safe.

Medications

Recommendations for use and dosages of medications to prevent and treat altitude illness are listed in Table 3.5.2.

Acetazolamide
Mechanism of action
When taken preventively, acetazolamide hastens acclimatization to high-altitude hypoxia, thereby reducing the occurrence and severity of AMS. It also enhances recovery if taken after symptoms have developed. The drug works primarily by inducing bicarbonate diuresis and metabolic acidosis, which counteracts the respiratory alkalosis, thereby stimulating ventilation and increasing alveolar and arterial oxygenation, especially during sleep. By using acetazolamide, high-altitude ventilatory acclimatization that normally takes 3–5 days takes only one day.

Dose
An effective dose for prophylaxis that minimizes the common side effects of paresthesia is 125 mg every 12 hours, beginning the day before ascent and continuing the first two days at altitude, and longer if ascent continues. Acetazolamide can also be taken episodically for symptoms of AMS, as needed. To date, the only dose studied for treatment is 250 mg (2 doses taken 8 hours apart), although the lower dosage used for prevention has anecdotally been successful. The pediatric dose is 2.5 to 5 mg/kg/day in divided doses, up to 125 mg, twice a day.

Adverse and allergic reactions
Allergic reactions to acetazolamide are uncommon. Acetazolamide is a sulfonamide derivative, but cross-sensitivity between antimicrobial sulfonamides and acetazolamide, a non-antimicrobial sulfonamide, has not been reported. Thus, people allergic to sulfa antibiotics can take acetazolamide. However, a history of anaphylaxis to any medication, or a history of multiple drug allergies, requires caution. Although not an adverse reaction, acetazolamide inhibits carbonic anhydrase, which ordinarily catalyzes the breakdown of carbonic dioxide on the tongue when drinking carbonated drinks. This allows the person to taste the carbon dioxide on their tongue, altering the taste of the drink.

Dexamethasone
Dexamethasone is effective for preventing and treating AMS and HACE and might prevent HAPE as well. Unlike acetazolamide, if the drug is discontinued at altitude before acclimatization, mild rebound can occur. Acetazolamide is preferable to prevent AMS while ascending, and dexamethasone generally should be reserved for treatment, usually as an adjunct to descent. The adult dose is 4 mg every 6 hours; rarely is it needed for more than 1–2 days. An increasing trend is to use dexamethasone for "summit day" on high peaks (e.g., Aconcagua and Kilimanjaro) to prevent abrupt altitude illness.

Ibuprofen
Recent studies have shown that taking ibuprofen 600 mg every 8 hours helps prevent AMS, although not quite as effectively as acetazolamide. Ibuprofen is available over the counter, inexpensive, and well tolerated.

Nifedipine

Nifedipine both prevents and ameliorates HAPE. For prevention, nifedipine is generally reserved for people who are particularly susceptible to the condition. The adult dose for prevention or treatment is 30 mg of the sustained-release version every 12 hours or 20 mg every 8 hours. Nifedipine is difficult to dose in children, and amlodipine is preferred in children under 50 kg.

Phosphodiesterase-5 inhibitors
Phosphodiesterase-5 inhibitors selectively lower pulmonary artery pressure, with less effect on systemic blood pressure than nifedipine. Tadalafil, 10 mg taken twice a day during ascent, can prevent HAPE. It is also being studied as a possible treatment.

Preventing severe altitude illness or death

The main point of instructing travelers about altitude illness is not to eliminate the possibility of mild illness but to prevent severe illness, need for evacuation, or death. Because the onset of symptoms and the clinical course are sufficiently slow and predictable, there is no reason for anyone to die from altitude illness unless they are trapped by weather or geography in situations where descent is impossible and treatment is inaccessible. Travelers can adhere to three rules to help prevent death or serious consequences from altitude illness:

1. Know the early symptoms of altitude illness (same as a hangover) and be willing to acknowledge when symptoms are present.
2. Never ascend to sleep at a higher altitude when experiencing symptoms of altitude illness, no matter how minor the symptoms seem.
3. Descend if the symptoms become worse despite rest or treatment at the same elevation.

For trekking groups and expeditions going into remote high-altitude areas, where descent to a lower altitude could be problematic, a pressurization bag (e.g., the Gamow bag) can be beneficial. A foot pump produces an increased pressure of 0.14 kg/cm2 (2 lb/in2), mimicking a descent of approximately 1,500–1,800 m (5,000–6,000 ft) depending on the starting elevation. The total packed weight of the bag and pump is about 6.5 kg (14 lb).

Preexisting medical conditions

Travelers with preexisting medical conditions must optimize their treatment and have their conditions stable before departure. In addition, these travelers should have plans for dealing with exacerbation of their conditions at high altitude. Travelers with underlying medical conditions (e.g., coronary artery disease, any form of chronic pulmonary disease or preexisting hypoxemia, obstructive sleep apnea [OSA], or sickle cell trait)—even if well-controlled—should consult a physician familiar with high-altitude medical issues before undertaking such travel (Table 3.5.3).

Healthcare professionals advising travelers should know that in most high-altitude resorts and cities, "home" oxygen is readily available, but in the United States, a prescription is required. Supplemental oxygen, whether continuous, episodic, or nocturnal, depending on the circumstances, is very effective at restoring oxygenation to low-altitude values and eliminates the risk of altitude illness and exacerbation of preexisting medical conditions.

Diabetes mellitus
Travelers with diabetes can travel safely to high altitudes, but they must be accustomed to exercise if participating in strenuous activities and should carefully monitor their blood glucose. Diabetic ketoacidosis can be triggered by altitude illness and can be more difficult to treat in people taking acetazolamide. Not all glucometers read accurately at high altitude.

Obstructive sleep apnea
Travelers with sleep disordered breathing who are planning high-altitude travel should receive acetazolamide. Those with mild to moderate OSA who are not hypoxic at home might do well without a continuous positive airway pressure (CPAP) device, while those with severe OSA should be advised to avoid high-altitude travel unless they receive supplemental oxygen in addition to their CPAP. Oral appliances for OSA can be useful adjuncts when electrical power is unavailable.

Pregnancy
There are no studies or case reports describing fetal harm among women who briefly travel to high altitude during their pregnancy. Nevertheless, healthcare professionals might be prudent to recommend that pregnant women do not stay at sleeping altitudes >3,050 m (>10,000 ft). Travel to high altitudes during pregnancy warrants confirmation of good maternal health and verification of a low-risk gestation. Advise pregnant travelers of the dangers of having a pregnancy complication in remote, mountainous terrain.

Radial keratotomy
Most people do not have visual problems at high altitude. At very high altitudes, however, some people who have had radial keratotomy procedures might develop acute farsightedness and be unable to care for themselves. Laser-assisted in situ keratomileusis (LASIK) and other newer procedures may produce only minor visual disturbances at high elevations.