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這篇文章的筆記本來放在這裡 [2018-05-23]AMS 急性高山病危險原因子
但文章實在太長了. 很難閱讀. 所以只好另開一篇.
這篇文章發表在 Rambam Maimonides Medical Journal
創這個期刊創刊於2010年7月 impact factor= 1.44
High-Altitude Illnesses: Physiology, Risk Factors, Prevention, and Treatment
放射科醫師?? Andrew T. Taylor, M.D.* Department of Radiology, Emory University School of Medicine, Atlanta, GA, USA
發表在以色列瑞本醫療中心期刊的"巨著"... 文章好長啊.
這裡的home elevation 不知道怎麼翻譯比較好. 住宿海拔?? ()風險因素包括家庭海拔、最高海拔、睡眠海拔、上升率、緯度、年齡、性別、身體狀況、運動強度、預先適應、基因構成和既往疾病。在海拔較高的地方，睡眠障礙可能會變得更加嚴重，精神表現會受損，並且可能會出現體重減輕。如果上升速度很快，乙酰唑胺可以降低患 AMS 的風險，儘管許多服用乙酰唑胺的高海拔旅行者仍會出現症狀。布洛芬可有效治療頭痛。下降可以迅速緩解症狀，如果可能的話，下降是強制性的，以控制可能致命的高原肺水腫和腦水腫綜合症。本綜述的目的是結合對特定風險因素、預防
高海拔病發生於不能適應海拔上升的人，影響了腦部與腦部的病變，最常見的病變是AMS。在柳葉刀期刊1976年的一篇《 Nuptse and Die 》充其量是邪惡的，最壞的時候是致命的，是一個要避免的實體” (翻成中文更看不懂了)
努子努子峰，鄰近聖母峰，西峰，通常在海拔 3000-5000 公尺會看到。
3000公尺，在很多滑雪旅館會到達這個海拔。氧氣分壓僅為海平面70%。
5000公尺。氧氣分壓僅海平面 50%
高海拔疾病包括在快速上升到高海拔後不久發生在未適應環境的個體中的肺部和腦部綜合症。這些綜合症中最常見的是急性高山病 (AMS)，在社論“See Nuptse and Die”中將其描述為“最好的情況下是卑鄙的，最壞的情況下是致命的，是一個需要避免的實體”。1 努子峰，意為西峰, 在珠穆朗瑪峰旁邊升起，通常從 3,000-5,000 米的海拔高度觀看（圖 1）。不包括南極洲，世界上只有 2.5% 的陸地面積在 3,000 米以上，但這些高度吸引了遊客、徒步旅行者、滑雪者和登山者，其中許多人居住在海平面附近。1 每年有數百萬遊客前往高海拔地區，並且，隨著生態旅遊和全球探險旅遊的發展，越來越多的各個年齡段的人都在遠足和攀登到非常高甚至極端的海拔高度（表 1）。在滑雪勝地常見的海拔高度 3,000 米處，氧分壓 (PO2) 僅為海平面值的 70% 左右；在 5,000 米處，該值降至 50%（表 2）。許多高海拔旅行者對他們的旅行準備不足，並且對相關風險一無所知。這篇綜述有兩個目的：首先是強調高原缺氧的基本生理反應，為理解高原疾病提供背景；第二個是討論具體的風險因素、預防、以及急性高山病 (AMS) 和可能致命的高原肺水腫和腦水腫綜合症的治療方案，以便醫生和醫療保健專業人員可以適當地建議旅行者登高到高原。評論按特定主題組織，以便讀者快速識別感興趣的領域。
氣壓, 蒸氣, 二次氧化碳
海平面氣壓 760 mmHg. 氧氣濃度20.94%。氣壓分壓159mmHg，
37度關節壓力和水蒸氣壓力47mmHg。與海拔無關。水蒸氣會設置換氣與氣。所以吸入的氣壓在海平面上為 149 mmHg。水蒸氣影響只佔整個大氣壓的6%。但。在高海拔。部分水蒸氣影響會逸變大。
聖母峰上。大氣壓僅 250 mmHg。水蒸氣影響19%的氣壓。更進一步降低低氣壓的取。
下面是我自己舉的例子。
同樣的水溫。水面的壓力越小。水氣越容易蒸發，如果在地球表面將水置放於一個攝氏37度的恆溫密閉空間，將水面上的空氣全部空氣瞬間傾吐。此時水面上氣壓為0，水會瞬間沸騰，隨著水面上蒸汽壓力上升，水汽騰的狀態會逐漸飽和，直到空氣的氣壓到7Hg 4 此時水的蒸發與凝結達到動態平衡。
(水蒸氣發會讓水溫下降, 在此假使用其他的加溫器, 將空氣間溫度維持37度恆溫)
BAROMETRIC PRESSURE, WATER VAPOR, AND CARBON DIOXIDE
大氣壓或大氣壓通常以 mmHg（汞）表示，但有時也以托表示，以紀念 Evangelista Torricelli（1608-1647 年），他是第一個證明大氣施加壓力並可以支撐汞柱的人。一毫米汞柱基本上相當於一托。在海平面，大氣壓力為 760 mmHg。乾燥空氣中氧氣（O2）的百分比為20.94%；因此，海平面的 O2 分壓為 159 mmHg (0.2094 × 760)。當吸入空氣時，它會變暖並充滿水蒸氣。在 37°C 時，無論海拔高度如何，肺部的飽和蒸氣壓均為 47 mmHg；由於水蒸氣置換了氧氣和氮氣，因此吸入氧氣的分壓為 149 mmHg (0.2094 × (760 – 47))。海平面時肺部的水蒸氣分壓僅佔總氣壓的 6%，但在高海拔地區水蒸氣變得越來越重要。在大氣壓僅為 250 毫米汞柱的珠穆朗瑪峰山頂，水蒸氣佔總大氣壓的近 19%，進一步減少了可用氧氣。 13
休息狀態。人體的二氫化碳分壓為40 mmHg。二次氧化碳也會調換一部分的大氣。因此。在海平面。受到二次氧化鋁。水蒸氣。呼吸道死肚，等的影響。最後肺泡的氣壓約為100 mmHg。過度換氣。會降低血中二氧化碳分壓。一步一步有提升氣壓的效果（在平地不明示）。高海拔。過度換氣現象會比明示，在聖母峰，吸入的空氣分壓僅為海平面29%。肺泡通氣增加了 5 的係數。極端的過度換氣可將二次氧化碳分壓降低至7-8 mmHg。僅正常值 1/5。因血中二氧化碳的減少。可提升肺泡內的空氣。維持35mmHg。足以讓登入者得以生存。
靜止時，肺中二氧化碳 (PCO2) 的分壓為 40 mmHg，這進一步取代了氧氣。儘管海平面吸入氧氣的分壓為 159 mmHg，但 CO2、水蒸氣和死腔的綜合作用將肺中的氧氣分壓 (PO2) 降低至大約 100 mmHg。過度通氣可使肺部 CO2 分壓降至 40 mmHg 以下，從而使 O2 分壓升高。這種影響在海拔高度被放大。在珠穆朗瑪峰的頂峰，吸入的 PO2 僅為其海平面值的 29%，肺泡通氣量增加了 5 倍。這種極端的過度通氣將肺泡 PCO2 降低至 7-8 mmHg，約為它的正常值。由於 PCO2 減少，肺泡 PO2 可以升高並維持在 35 mmHg 附近，
缺氧通氣反應和呼吸控制
在高海拔地區，通氣頻率和深度會增加，以補償氧分壓 (PO2) 的降低。這種通氣增加稱為缺氧通氣反應 (HVR)，部分由位於頸總動脈分叉處的頸動脈體介導，對血液中的溶解氧敏感。然而，呼吸的主要刺激因素並不是缺氧。它是高碳酸血症，血液中二氧化碳含量的增加。這種刺激是由位於髓質中的強化學感受器介導的。儘管血腦屏障將這些髓質化學感受器與動脈血隔開，但血腦屏障可滲透 CO2。二氧化碳 (PaCO2) 和氫離子濃度（酸血症）的動脈壓升高會刺激呼吸，
通過碳酸酐酶的作用，外周組織中產生的 CO2 與水結合形成碳酸 (H2CO3)，並在其中迅速離解成氫和碳酸氫根離子，如下所示： 碳酸酐酶 (1) 的反應速度是最快的
之一所有酶，其速率通常受底物擴散速率的限制；離子解離 (2) 不受酶加速的影響，幾乎是瞬時的。在 CO 2濃度高的組織中 ，反應向右進行，導致碳酸氫根和氫離子的產生增加。氫離子被脫氧血紅蛋白緩衝，脫氧血紅蛋白結合氫離子並將它們輸送到肺部。在肺中，CO 2 被去除時，血紅蛋白與氧的結合迫使氫離子脫離血紅蛋白，反應逆轉。血清 pH 值與碳酸氫鹽/PaCO 2
比率成正比 。儘管PaCO 2取決於CO 2 產生和CO 2消除 之間的平衡，但它高度依賴於CO 2消除 的速率 。
過度換氣會加速 CO2 的消除，並通過降低 PaCO2 和升高血液的 pH 值而產生呼吸性鹼中毒。PaCO2 的降低和由此產生的鹼中毒共同作用於髓質化學感受器以減少通氣。因此，對缺氧的通氣反應 HVR 在維持氧飽和度方面變得尤為重要，因為正常的 CO2 介導的通氣驅動因低碳酸血症而減弱。到達海拔高度時 HVR 的強度和速度因人而異，HVR 未能增加會導致低氧血症和 AMS 的發展。 17 腎臟對高海拔缺氧的
適應
如前一節所述，對高原缺氧的最初反應是由過度換氣產生的呼吸性鹼中毒。幾分鐘內，腎臟對鹼中毒的反應是增加碳酸氫根離子的排泄；這種腎臟作用可以持續數小時或數天，並起到糾正鹼中毒和使血清 pH 恢復正常值的作用。
腎臟也通過分泌促紅細胞生成素來應對缺氧。促紅細胞生成素導致紅細胞量增加，血液攜氧能力增加（溶解氧僅佔攜氧能力的2%左右）；然而，需要幾天時間才能測量到紅細胞生成率的增加，並且該過程需要數週或數月才能完成。 14,18 對於短期上升，促紅細胞生成素介導的紅細胞量增加並不重要，儘管這對於長途探險很重要。血細胞比容，而不是總血紅蛋白，在短期上升期間因缺氧介導的利尿作用引起的血漿容量減少而增加；血細胞比容的升高會增加每 100 毫升血液的攜氧能力。 17–20
海拔高度的血紅蛋白飽和度曲線
當血液暴露在肺部的高氧壓力下時，氧氣會迅速並可逆地與血紅蛋白結合形成氧合血紅蛋白。在 PO2 約為 100 mmHg 的海平面，血紅蛋白 (SaO2) 的動脈氧飽和度為 95%–98%。氧-血紅蛋白解離曲線（圖 2）顯示血紅蛋白飽和度隨 O2 分壓降低而發生的變化。21 其呈 S 形是因為血紅蛋白分子包含四個血紅素基團，每個血紅素基團與一個 O2 分子發生反應；第一個血紅素基團的氧化增加了 O2 對其餘基團的親和力。這種特有的形狀有利於肺部的氧氣負荷和組織中的氧氣釋放。隨著海拔的升高，由於氧-血紅蛋白解離曲線的上部部分相對平坦，因此與 PO2 相比，SaO2 最初保持良好。隨著高度的增加，氧合血紅蛋白解離曲線的陡峭部分變得更加重要，導致 SaO2 的下降速度更快。在海拔 8,400 米的珠穆朗瑪峰，動脈血氧分壓 (PaO2) 降至 25 mmHg，血紅蛋白飽和度僅為 50%。
活躍代謝組織的氧氣需求增加導致 CO2 和氫離子濃度增加，伴隨著局部溫度升高和 2,3-二磷酸甘油酸水平升高，所有這些都使氧-血紅蛋白解離曲線向右移動，促進組織中的氧氣釋放，而在相反的條件下向左移動。在高海拔地區，過度換氣引起的急性呼吸性鹼中毒會導致氧-血紅蛋白解離曲線向左移動，增加任何給定 PaO2 的動脈飽和度。這種左移改善了肺部的氧氣吸收，而不是損害了組織中的卸載。在肺負荷非常高的極度缺氧條件下，
AMS：臨床特徵
高海拔缺氧會導致睡眠障礙、智力受損、體重減輕和運動能力下降。
睡覺
人類從海平面迅速上升到海拔 2,500 米以上的高度睡覺時，由於動脈血氧水平低和周期性呼吸的共同作用，睡眠數量和質量通常會出現紊亂。週期性呼吸，呼吸頻率和/或潮氣量的振盪，是正常健康成年人中的一種有據可查的現象。 24 在快速上升到高海拔後，睡眠期間的周期性呼吸幾乎是普遍的，並導致令人不安的夢想、頻繁的覺醒、覺醒、以及在高海拔地區經常經歷的睡眠質量差的主觀感覺。25,26 週期性呼吸的基本模式因缺氧而加劇，並因缺氧通氣反應增加而加劇。由此產生的過度通氣會導致低二氧化碳性鹼中毒，這會抑制通氣甚至達到呼吸暫停的程度。
精神表現和腦萎縮
大腦通常佔總耗氧量的 20%。在中度至重度缺氧的高海拔條件下，精神表現會受損。14 編碼和短期記憶的損害在 6,000 米以上尤為明顯，準確度和運動速度的變化發生在較低海拔。 27 更令人擔憂的是研究表明，業餘和專業登山者在攀登極高和極端海拔高度時，都有發生皮層下病變和皮層萎縮的風險。
高海拔減肥
高海拔暴露可能會導致體重顯著下降，這似乎是絕對海拔高度和暴露持續時間的函數。體力活動、AMS 引起的噁心和缺乏可口食物都會導致在高海拔地區體重減輕，而胃腸炎、上呼吸道感染和低溫會進一步加劇體重減輕。海拔低於 4,000 米時，最初體重減輕約 3%，在海拔 5,000 至 8,000 米的長期停留期間，體重減輕高達 15%。30 最初體重減輕可能反映了多尿和水分流失。除了最初的利尿作用之外，體重減輕似乎可以通過保持身體活動和充足的飲食攝入來預防；很遺憾，一些徒步旅行公司在食物的質量和種類上吝嗇，並且由於未能提供足夠的飲食而導致體重減輕。5,000 米以上的體重減輕可能是不可避免的，主要是與活動水平無關的肌纖維萎縮的結果，可能與缺氧對蛋白質代謝的直接影響有關
身體狀況和運動
運動能力隨海拔升高而降低。肺泡氧分壓略高於動脈血氧分壓，隨著心輸出量增加、毛細血管傳輸時間縮短和靜脈氧需求增加，這種肺泡-動脈壓差在運動過程中逐漸擴大。在海平面，這種由運動引起的壓差伴隨著通氣反應，這種反應的上升與氧氣需求的增加不成比例；這種增強的通氣反應通常足以維持動脈 PO2 並防止低氧血症的發展。 32 然而，在高海拔缺氧條件下，通氣反應不再足以防止運動引起的動脈血氧飽和度下降；甚至輕度動脈血氧飽和度下降 (<
當與快速上升相結合時，劇烈運動和過度勞累是 AMS 的危險因素。在減壓室模擬海拔增加 3,000 米的受試者的對照研究中，運動顯著降低了動脈飽和度 (SaO2) 並增加了 AMS 症狀評分。 34 身體調節在預防 AMS 方面的效果更難評估，因為那些身體狀況良好的人傾向於進行更劇烈的運動和更快的上升，這兩者都是 AMS 的危險因素。然而，數據表明，身體狀況良好的受試者患 AMS 的風險可能與訓練程度較低的人相似
AMS：風險因素
AMS 與許多潛在的風險因素有關，包括家庭海拔、最大睡眠海拔、上升速度、緯度、年齡、性別、身體狀況、運動強度、血紅蛋白飽和度、預適應、先前在海拔高度的經歷、基因構成-起來，和先前存在的疾病。
家庭海拔和最大睡眠高度
從海平面上升的旅行者比生活在高海拔地區的人患 AMS 的風險更高。科羅拉多滑雪勝地的一項研究說明了這種差異，該研究表明，從海平面抵達的居民患 AMS 的風險為 27%，而居住在 1,000 米以上的居民患 AMS 的風險為 8.4%。3 在住在瑞士阿爾卑斯山小屋的登山者中，AMS 的患病率從 2,850 米處的 9% 到 4,559 米處的 53%（表 2）。5 這些結果與住在尼泊爾茶館的徒步旅行者中 AMS 的患病率相當範圍從 3,000–4,000 米時的 10% 到 4,500–5,000 米時的 51%（表 2）。4 有趣的是，在這項研究中，AMS 的患病率從 4,500–5,000 米時的 51% 下降到高於 5 時的 34%，
上升速度和乞力馬扎羅山
快速上升速度是 AMS 發展的一個重要因素。 3 與攀登乞力馬扎羅山的徒步旅行者相比，尼泊爾珠穆朗瑪峰地區的徒步旅行者似乎具有更慢的上升速度和更低的 AMS 患病率上升速度更快。4,6,37,38 在攀登到極高海拔的登山者中，幾天的適應差異會對 AMS 的患病率、症狀嚴重程度和登山成功產生重大影響。 36
乞力馬扎羅山海拔 5,895 米，是世界上從山腳到山頂的最高獨立山峰。它很受歡迎，交通方便，而且它靠近赤道的位置提供了將登頂嘗試與到鄰近野生動物保護區的野生動物園相結合的選擇。每年有 20,000 名登山者嘗試登頂。6 登頂的標準路線（可能需要一些爬行的 Western Breech 除外）沒有技術性，任何身體狀況良好的人都可以徒步登頂。儘管攀登具有非技術性質，但在這座山上還是發生了無數死亡事件。6 為了降低成本並有效競爭，徒步旅行公司通常安排相對快速的攀登，留下有限的適應時間。
緯度
緯度影響氧氣可用性、血紅蛋白飽和度和發生 AMS 的風險。由於自轉，地球在赤道處凸起；因此，赤道的大氣壓力和 PO2 均高於兩極。在阿拉斯加中部德納利峰 6,194 米的山頂，大氣壓力相當於喜馬拉雅山 6,900 米山峰山頂的大氣壓力。 39 由於這種影響，在同等海拔高度，乞力馬扎羅山的登山者缺氧較少（ 3°S) 甚至珠穆朗瑪峰 (23°N) 比 Denali (63°N)。如果珠穆朗瑪峰與麥金利峰處於同一緯度，那麼在沒有補充氧氣的情況下就無法攀登。
性別和年齡性別與年齡。男性都可能得到 AMS。但有些研究發現女性性得到 AMS 機率較高。百年大的人AMS機率並沒有更高。事情實際上有一篇研究發現。18-19歲的人。去科羅拉多滑雪旅館 45% 得到AMS。60-87 歲的人，僅 16% 得到 AMS。顯然是世紀大的這組AMS機率反應而下降。但這項研究並沒有做到控制。也許是年輕人運動強度大。所以得到AMS機率上升。孩子的臨床研究並不多。但發生率跟成人似的。
男性和女性患 AMS 的風險似乎相同，4,5,39 儘管一些觀察性研究表明女性的風險略高。3 老年人患 AMS 的風險似乎沒有增加；4,36 事實上，一個研究表明，年輕人可能面臨更高的風險。在科羅拉多州的滑雪勝地，18 至 19 歲的人群 AMS 發病率為 45%，而 60 至 87 歲人群的這一比例僅為 16%3。低齡人群的運動強度。目前尚無針對兒童的 AMS 對照試驗，但發病率似乎與成人相似。 40
運動強度
如上所述，隨著運動量的增加，肺泡-動脈壓差逐漸擴大，導致高原血紅蛋白飽和度降低，同時 AMS 的風險和嚴重程度增加。 32,34 為了降低 AMS 的風險，劇烈運動和過度勞累快速上升到高海拔後應立即避免。
動脈氧合血紅蛋白飽和度
早期低氧血症，即 SaO2 的降低幅度大於給定海拔高度的預期值，是發生 AMS 的一個危險因素。 41-43 早期低氧血症似乎是彌散障礙或靜脈混合的結果，可以用脈搏血氧計監測（圖 3）。41–43 應建議患有早期低氧血症的個體避免劇烈運動，如果繼續上升，則應緩慢上升。脈搏血氧儀相對便宜，通常由徒步旅行公司攜帶，以監測 AMS 症狀惡化的個體的 SaO2；但是，如果要在非常高或極端的海拔高度使用它們，則檢查校準很重要。低於 83% 的 SaO2 測量值的準確度和精密度可能與飽和度較高的測量值不同。
脈搏血氧計有一對小二極管，可以通過患者身體的半透明部分（例如指尖或耳垂）發出不同波長的光；根據對兩種波長的吸收差異，儀器可以區分脫氧血紅蛋白和氧合血紅蛋白。為了正常工作，脈搏血氧計必須檢測脈搏，因為它經過校準以檢測動脈血管隨心跳的脈動擴張和收縮。凍傷、手指冰冷或血容量不足的受試者可能會出現讀數不准確的情況。
之前的 AMS 和之前的海拔高度暴露
先前的 AMS 病史是隨後暴露於可比海拔高度後發生 AMS 的重要預測因素。 45 相反，近期或極端海拔暴露史與 AMS 的較低風險（6,962 米）相關。 45,46 自我選擇是可能是一個重要因素；那些在沒有發展 AMS 的情況下容忍和享受高山的人更有可能重複這種經歷。
遺傳適應
幾千年來，人類一直在高海拔地區生活和工作。也許最著名的高海拔人口是喜馬拉雅山的夏爾巴人和藏人，以及安第斯山脈的蓋查人和阿亞馬拉人。安第斯山脈人群的血紅蛋白濃度高於喜馬拉雅高地人群，而喜馬拉雅山脈人群對缺氧環境的反應更高，通氣反應更高。47 這些差異可能具有遺傳因素，儘管尚未確定具體的遺傳差異。
許多細胞功能（例如蛋白質合成）會因缺氧而下調，但某些子集會上調。上調亞群中最突出的是由缺氧誘導因子 1.48 控制的基因家族。缺氧誘導因子 1 作為氧穩態的全局調節劑，促進 O2 輸送和適應 O2 剝奪。第一個發現的缺氧依賴性基因表達的例子是促紅細胞生成素，它會導致血細胞比容和 O2 攜帶能力增加。另一個可能有助於高海拔表現的遺傳因素是血管緊張素轉換酶基因的多態性，這在精英登山者和耐力運動員中似乎比在普通人群中更為普遍。 49 個體對高海拔的易感性差異很大。高原障礙; 有些人在海拔低至 3,000 米的情況下會出現危及生命的高原腦水腫或肺水腫並發症，而其他人則可以在沒有補充氧氣的情況下爬升至 8,000 米。遺傳影響仍然是一個活躍的研究領域
既往疾病 患有
潛在心髒病或肺病的休閒旅行者、徒步旅行者和滑雪者經常尋求有關高海拔旅行的建議。無症狀的冠心病患者通常情況良好，但避免劇烈運動可能是謹慎的做法；心力衰竭患者應避免高原缺氧。51 嚴重貧血和鐮狀細胞病也是高原旅行的禁忌症。51 對肺部疾病患者的建議取決於基礎疾病、嚴重程度和預期的高度和活動水平；具體建議載於對該主題的廣泛審查。
高原腦水腫
高原腦水腫 (HACE) 可能是 AMS 的連續體。AMS 通常是自限性的，而 HACE 可能是致命的。應仔細監測路易斯湖得分高的個體是否出現共濟失調、意識模糊和幻覺的跡象，這些跡象可能標誌著 HACE 的發作。HACE 是一種臨床診斷，包括 AMS 或高原肺水腫患者的共濟失調和意識改變。AMS 患者在症狀消失之前不應上升；如果症狀無法解決，他們應該下降。如果可能的話，患有 HACE 的人應該立即下山，並且絕不能在無人陪伴的情況下下山。
導致高原腦水腫的確切過程尚不清楚，儘管水腫可能是細胞外的，由於血腦屏障滲漏（血管源性水腫），而不是細胞內的，由於細胞腫脹（細胞毒性水腫）。53 血管源性水腫優先沿白質束擴散，而細胞毒性水腫影響灰質和白質。HACE 患者的 MRI 研究表明，大多數白質區域有強烈的 T2 信號，特別是胼胝體壓部，但沒有灰質異常。53 對壓部和胼胝體的偏愛令人費解。壓部可能比周圍組織更容易擾動細胞流體力學。脾部 MRI 異常不僅限於 HACE 患者，還發生在酒精使用、感染、低血糖和電解質異常等情況下；54 在這些病例中，壓部異常也與意識模糊和共濟失調有關，而這組症狀可能是壓部水腫的特徵。HACE 的死因是腦疝。
地塞米松（見下文）可用於治療 AMS 和 HACE，但與乙酰唑胺不同，地塞米松不會促進適應環境，並可能給人一種錯誤的安全感。是輔助下降的極佳救援藥物。55, 56 如果無法下降，氧氣和便攜式充氣高壓艙（圖 4) 提高氧飽和度，可有效治療 HACE 或高原肺水腫患者。
充氣高壓艙通常由將客戶帶到高海拔地區的徒步旅行公司攜帶；這些袋子重約 6.5 千克，展開後呈圓柱形，大到足以容納一個人（圖 4）。通過用腳踏泵給袋子充氣，有效海拔高度最多可降低 1,500 米（5,000 英尺）。當人在袋子裡時，必須連續使用腳踏泵以提供新鮮氧氣並排出二氧化碳。
高原肺水腫
高海拔肺水腫 (HAPE) 是快速上升到高海拔的潛在致命後果。早期診斷可能很困難，因為許多早期症狀（呼吸急促、呼吸急促、心動過速、動脈飽和度降低、疲勞和咳嗽）經常出現在高海拔地區的未受影響的登山者身上，特別是在寒冷、乾燥或多塵的環境中。高原肺水腫的鑑別特徵包括無力性疲勞、輕微呼吸困難進展為靜息時呼吸困難、端坐呼吸，以及因咯血而從乾咳進展為咳痰並伴有粉紅色泡沫痰。HAPE 也可能伴有發熱，其存在並不意味著感染；除非有其他症狀或胸片提示肺炎，否則不需要立即使用抗生素。 59
HAPE 的發作通常較晚，通常發生在到達高海拔地區後 2-4 天；它之前並沒有統一出現 AMS。14 HAPE 在海拔超過 3,000 米時最常見，52 但 HAPE 可以而且確實發生在較低海拔。在 7 年的時間裡，科羅拉多州一個海拔 2,500 米的滑雪勝地報告了 47 例 HAPE。60
高原肺水腫的發病機制尚待研究；然而，它可能是由缺氧引起的正常肺血管收縮引起的肺動脈壓升高引起的。HAPE 患者的肺部對缺氧反應增強，肺動脈壓力過度升高，並且通過降低肺動脈壓力的藥物干預得到改善。 61-63 在一部分個體中，中度至劇烈運動可能起到促進作用，因為運動會單獨導致肺動脈壓力升高，這種效應可能會加重缺氧導致的壓力升高。
令人信服的證據表明 HAPE 是一種靜水壓引起的滲透性滲漏伴有輕度肺泡出血。62,64,65 提出了兩種解釋。一是缺氧性肺血管收縮不均勻；因此，由擴張的小動脈供血的肺毛細血管暴露在高壓下，導致毛細血管壁受損（應力衰竭）並導致含有紅細胞的高蛋白水腫液滲漏。 4 第二種解釋假設肺毛細血管壓力增加是由於62,65 無論機制如何，使用肺血管擴張劑硝苯地平成功預防和治療高原肺水腫表明肺動脈高壓對於高原肺水腫的發展至關重要。 63,66
沒有評估治療策略的隨機對照試驗。氧氣、休息和下降通常是一致同意的。 59,66 當患者對保守措施無反應或在偏遠地區發生 HAPE 時，推薦硝苯地平，最初口服 10 mg，然後每 12-10 個月口服 30 mg 緩釋製劑。 24 小時 66 磷酸二酯酶抑製劑（例如他達拉非）已被證明可以預防易感個體 HAPE 67，並且在患者管理中也可能有效。一些醫生現在採用硝苯地平和磷酸二酯酶抑製劑的聯合療法，68 儘管這些都是超說明書使用。如果無法下降，建議使用便攜式高壓艙。
AMS：預防和治療
用於預防和管理 AMS 的藥物包括乙酰唑胺、地塞米松、磷酸二酯酶抑製劑和鎮痛藥。預防 AMS 的策略包括預先適應環境、大量飲水和高碳水化合物飲食。
乙酰唑胺
乙酰唑胺是一種有效的碳酸酐酶抑製劑；它在預防和改善 AMS 方面的功效已得到充分證明，儘管關於最佳劑量仍存在爭論。 69–71 最近在尼泊爾珠穆朗瑪峰地區進行的一項雙盲、隨機、安慰劑對照研究表明，每天兩次 125 毫克是有效的。與 375 mg 每天兩次一樣有效預防 AMS。69 在這項研究中，服用乙酰唑胺的受試者中 AMS 的平均發生率約為 22%，而服用安慰劑的受試者為 51%。乙酰唑胺不是靈丹妙藥；相當大比例的服用乙酰唑胺的受試者仍然會發展為 AMS。事實上，在攀登速度往往比尼泊爾更快的乞力馬扎羅山上，服用乙酰唑胺（250 毫克，每天兩次）的人群中 AMS 的發生率為 55%，而對照組/安慰劑組為 84%。72 雖然從未確定精確劑量和推薦的治療持續時間，56 一種合理的預防方法是從上升前 1 天開始每天兩次 125 毫克，並在達到最大高度後持續 2 天或直到開始下降；如果上升速度很快，每天兩次 250 毫克可能更有效，但產生副作用的風險更大。對於兒童，乙酰唑胺的推薦劑量為每 12 小時口服一次 2.5 mg/kg，最大劑量為 250 mg73；48 小時的治療通常足以緩解症狀。 40 每天兩次 250 毫克可能更有效，但產生副作用的風險更大。對於兒童，乙酰唑胺的推薦劑量為每 12 小時口服一次 2.5 mg/kg，最大劑量為 250 mg73；48 小時的治療通常足以緩解症狀。 40 每天兩次 250 毫克可能更有效，但產生副作用的風險更大。對於兒童，乙酰唑胺的推薦劑量為每 12 小時口服一次 2.5 mg/kg，最大劑量為 250 mg73；48 小時的治療通常足以緩解症狀。 40
乙酰唑胺增加每分鐘通氣量、改善動脈血氣和減輕 AMS 症狀的實際機制仍然知之甚少。 71 乙酰唑胺的功效歸因於抑制腎臟中的碳酸酐酶，導致碳酸氫鹽尿和代謝性酸中毒，它抵消了呼吸引起的鹼中毒，並允許化學感受器對海拔高度的缺氧刺激做出更充分的反應。然而，可能涉及其他機制：碳酸氫鹽最終會降低腦脊液 (CSF) 碳酸氫鹽濃度，從而降低 CSF pH 值並刺激通氣。71 膜結合的碳酸酐酶同工酶存在於包括大腦在內的幾乎所有毛細血管床的管腔側，並且可以被低劑量的乙酰唑胺抑制，導致局部組織 CO2 滯留約 1–2 mmHg。 71,74鑑於中樞化學感受器對 CO2 的高通氣反應性，大腦中 CO2 分壓的這種輕微增加可能會刺激通氣發生深刻變化。 74 事實上，紅細胞和血管內皮碳酸酐酶的抑制已被證明會導致幾乎立即的滯留所有組織中的 CO2 作為交換和運輸的正常機制減弱。由此產生的組織酸中毒被認為是與碳酸酐酶抑制相關的過度換氣的重要刺激因素。 71，
乙酰唑胺是一種磺胺類藥物；對磺胺類抗生素有過敏反應的患者更有可能對非抗生素磺胺類藥物產生後續過敏反應，但這種關聯似乎是由於對過敏反應的易感性，而不是與基於磺胺類藥物的特定交叉反應75 然而，一般建議是已知對磺胺類藥物過敏的患者應避免使用乙酰唑胺。56 乙酰唑胺最常見的副作用是外周和口腔周圍感覺異常，但食慾不振和噁心也有報導。碳酸酐酶在口腔中的抑製作用也會影響碳酸飲料的口感。更高的劑量（250 毫克，每天兩次或三次）與更大的副作用相關。最後，
地塞米松 地
塞米鬆在預防 AMS 方面可能不如乙酰唑胺有效，70 但它作為 AMS 的緊急治療是有效的，初始劑量為 4-10 mg，隨後每 6 小時 4 mg。 55,56,76,77 地塞米松降低AMS 症狀學但不改善與高海拔暴露相關的客觀生理異常；患有嚴重 AMS 的受試者在用地塞米松治療後可能在症狀學上有顯著反應，但在 CT 掃描中仍顯示腦水腫。77 目前，只有在不可能下降或促進疏散工作中的合作時才推薦使用地塞米松。
磷酸二酯酶抑製劑
一氧化氮合成減少可能是 HAPE 的促成因素。一氧化氮是一種在肺血管內皮中產生的血管擴張劑，由於局部磷酸二酯酶 (PDE) 的活性，其半衰期較短；因此，PDE 抑製劑可增強一氧化氮的作用。5-PDE 抑製劑西地那非（偉哥）可減輕靜息和運動後急性暴露於低壓缺氧引起的肺動脈高壓，78防止 高原引起的肺動脈高壓的發展，並改善氣體交換，限制高原引起的低氧血症和運動表現下降。79 他達拉非已被證明可以預防易感個體的 HAPE，67 這類藥物在治療 HAPE 患者方面顯示出希望。
對乙酰氨基酚和布洛芬
對乙酰氨基酚和非甾體類抗炎藥（如布洛芬和阿司匹林）通常可有效緩解與 AMS 相關的
頭痛
避免脫水很重要，尤其是因為在高海拔地區呼吸會損失大量水分。雖然缺水會降低高海拔地區的有氧運動能力，但它似乎不會增加 AMS 的患病率或嚴重程度。82 然而，人們認為缺水會增加 AMS 的風險，而過度飲水可以預防或治療這種疾病。 83 一些徒步領隊甚至敦促客戶飲用過量的水以避免或改善 AMS，但這一建議沒有科學依據。 66,84 這種信念可能源於對少女峰 (3,471 m) 的觀察，在那裡註意到排尿量最大的新來者比排尿量最少的人更能耐受海拔高度。83 這一觀察結果可能導致了這樣的假設，即大量飲水會導致利尿並預防 AMS。然而，在高海拔地區出現的早期利尿是對缺氧的反應，而不是過量的液體消耗；AMS 的發展與抗利尿激素血漿濃度升高和體液瀦留有關
預適應和海拔模擬
預先適應，即在進行更高海拔之前在高海拔地區停留一段時間，可以降低發生 AMS 的可能性。46 在高海拔地區生活並在低海拔地區進行訓練可以提高各種能力的運動員的表現；主要機制是促紅細胞生成素的增加，這直接導致紅細胞量的增加。紅細胞量的增加允許更多的氧氣輸送到組織，增加最大耗氧量，並提高運動能力。 85,86 對於高海拔旅行者或休閒登山者來說，預先適應通常是不切實際的，“活得高，訓練低”的方法不是大多數運動員的選擇。
最簡單的間歇性低氧訓練策略是在休息條件下呼吸氧分壓降低的空氣；這個策略很簡單，但未解決的變量是最佳會話次數、每個會話的最佳長度以及上升前會話的時間安排。目前，尚未定義一組可重複降低 AMS 可能性的靜息、常壓、低氧訓練參數。一種更複雜的方法是使用高度模擬系統，該系統可以安全地減少房間或帳篷中的氧氣含量。該系統創造了一個便攜的低氧環境，非常適合“生活高，訓練低”的環境，現在被用於世界各地的奧林匹克訓練中心。
碳水化合物
在急性缺氧暴露前 40 分鐘攝入純碳水化合物已被證明可使血紅蛋白飽和度提高 4%；然而，這種效果會在 150 分鐘後消失，並且碳水化合物消耗在改善氧合作用方面的任何優勢僅適用於碳水化合物被消化的時期。 89 這種效果取決於代表二氧化碳比率的呼吸商 (RQ)排泄到所利用的氧氣量；該比率的值取決於食物的碳含量，通常約為 0.85，但范圍從 0.7（純脂肪）到 1.0（純碳水化合物）。如下式所示，碳水化合物的代謝比脂肪的代謝產生更高的PAO2：
PAO2 = PiO2 - PaCO2/RQ
其中 PAO2 是肺泡中的氧分壓，PiO2 是吸入氧分壓，PaCO2 是二氧化碳分壓。較高的 PAO2 將導致較高的血紅蛋白氧飽和度。實際上，碳水化合物的新陳代謝比蛋白質或脂質的新陳代謝產生更多的 CO2；90 增加的 CO2 產生對呼吸中樞提供了額外的刺激。
概括
AMS 的典型症狀包括頭痛、食慾不振、睡眠障礙、噁心、疲勞和頭暈，這些症狀在快速上升到高海拔後不久就會出現。高海拔缺氧會導致睡眠障礙、智力受損、體重減輕和運動能力下降。影響 AMS 風險的因素包括家庭海拔、最大海拔、睡眠海拔、上升速度、緯度、運動強度、預適應、先前在海拔高度的經驗和基因構成。症狀通常可以通過休息和延遲進一步上升直到症狀消失來緩解；如果症狀嚴重，可以通過下降到較低的高度來迅速緩解。每天兩次劑量為 125 mg 的乙酰唑胺可降低攀登速度相對較慢的地區（例如尼泊爾珠穆朗瑪峰地區）AMS 的發病率和嚴重程度；在這些條件下，更高的劑量似乎並不更有效，但在乞力馬扎羅山等山區出現的更快速上升過程中可能是有利的。AMS 可能會發展為高原腦水腫 (HACE)，並且在沒有 AMS 的情況下可能會發生高原肺水腫 (HAPE)。這兩種情況都是醫療緊急情況；如果可能，初始管理應包括下降、補充氧氣，以及在 HACE 的情況下，地塞米松。硝苯地平和磷酸二酯酶可能對治療 HAPE 有效。懷疑有這兩種情況之一的人不應該單獨下山。
Risk factors include home elevation, maximum altitude, sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, pre-acclimatization, genetic make-up, and pre-existing diseases. At higher altitudes, sleep disturbances may become more profound, mental performance is impaired, and weight loss may occur. If ascent is rapid, acetazolamide can reduce the risk of developing AMS, although a number of high-altitude travelers taking acetazolamide will still develop symptoms. Ibuprofen can be effective for headache. Symptoms can be rapidly relieved by descent, and descent is mandatory, if at all possible, for the management of the potentially fatal syndromes of high-altitude pulmonary and cerebral edema. The purpose of this review is to combine a discussion of specific risk factors, prevention, and treatment options with a summary of the basic physiologic responses to the hypoxia of altitude to provide a context for managing high-altitude illnesses and advising the non-acclimatized high-altitude traveler.
高海拔疾病發生於未能適應海拔上升的人, 影響了肺部與腦部的症狀, 最常見的症狀是AMS.
在lancet期刊 1976年的一篇文章 "See Nuptse and Die"期刊編輯描述為 “vile at best, fatal at worst and an entity to be avoided”
Nuptse努子峰, 鄰近聖母峰, 西峰, 通常在海拔 3000-5000 公尺會看到.
3000 公尺, 在很多滑雪旅館會達到這個海拔. 氧氣分壓僅為海平面 70%.
5000 公尺. 氧氣分壓僅海平面 50%
High-altitude illnesses encompass the pulmonary and cerebral syndromes that occur in non-acclimatized individuals shortly after rapid ascent to high altitude. The most common of these syndromes is acute mountain sickness (AMS) which is described in the editorial, “See Nuptse and Die”, as “vile at best, fatal at worst and an entity to be avoided”.1 Nuptse, meaning west peak, rises next to Mount Everest and is commonly viewed from elevations ranging from 3,000–5,000 meters (Figure 1). Excluding Antarctica, only 2.5% of the world’s land mass lies above 3,000 m, yet these heights attract the tourist, hiker, skier, and mountaineer, many of whom dwell near sea-level.1 Millions of visitors travel to high altitudes every year, and, with the growth of ecotourism and global adventure travel, ever-increasing numbers of people of all ages are hiking and climbing to very high and even extreme altitudes (Table 1). At 3,000 m, an altitude commonly encountered in ski resorts, the partial pressure of oxygen (PO2) is only about 70% of the value at sea-level; at 5,000 m, this value falls to 50% (Table 2). Many high-altitude travelers will be poorly prepared for their trip and naive about the associated risks. This review has two purposes: the first is to highlight the basic physiologic responses to high-altitude hypoxia to provide a context for understanding high-altitude illnesses; the second is to discuss specific risk factors, prevention, and treatment options for acute mountain sickness (AMS) and the potentially fatal syndromes of high altitude pulmonary and cerebral edema so that physicians and health care professionals can appropriately advise travelers ascending to high altitude. The review is organized by specific topics to allow the reader to quickly identify areas of interest.
氣壓, 水蒸氣, 二氧化碳
海平面氣壓 760 mmHg. 氧氣濃度 20.94%. 氧氣分壓 159mmHg,
37度肺部飽和水蒸汽壓 47 mmHg. 與海拔無關. 水蒸氣會置換氧氣與氮氣. 所以吸入的氧氣分壓在海平面為 149 mmHg. 水蒸氣影響僅占整個大氣壓的 6%. 但. 在高海拔. 肺部水蒸氣影響會逐漸變大.
聖母峰上. 大氣壓僅 250 mmHg. 水蒸氣影響 19% 的氣壓. 更進一步降低氧氣的取得.
下面是我自己舉的例子.
同樣的水溫. 水面的壓力越小. 水氣越容易蒸發, 如果在地球表面將水置放在一個攝氏37度的恆溫密閉空間, 將水面上的空間所有空氣一瞬間都抽走. 這時候水面上氣壓為 0 , 水會瞬間沸騰, 隨著水面上蒸氣壓上升, 水沸騰的狀態會逐漸緩和, 直到空間的氣壓到達 47 mmHg 為止. 此時水的蒸發與凝結達到動態平衡.
(水蒸發會讓水溫下降, 在此假設使用另外的加溫器, 將空間溫度維持37度恆溫)
BAROMETRIC PRESSURE, WATER VAPOR, AND CARBON DIOXIDE
Barometric or atmospheric pressure is usually expressed in mmHg (mercury) although it is occasionally expressed in torr in honor of Evangelista Torricelli (1608–1647) who was the first person to demonstrate that the atmosphere exerts a pressure and can support a column of mercury. One mmHg is essentially equivalent to one torr. At sea-level, the barometric pressure is 760 mmHg. The percentage of oxygen (O2) in dry air is 20.94%; consequently, the partial pressure of O2 at sea-level is 159 mmHg (0.2094 × 760). When air is inhaled, it is warmed and saturated with water vapor. At 37°C, the saturated vapor pressure in the lungs is 47 mmHg regardless of altitude; because water vapor displaces oxygen and nitrogen, the partial pressure of inspired oxygen is 149 mmHg (0.2094 × (760 – 47)). The partial pressure of water vapor in the lungs at sea-level accounts for only 6% of the total barometric pressure, but water vapor becomes increasingly important at high altitudes. On the summit of Mount Everest, where the barometric pressure is only 250 mmHg, water vapor accounts for nearly 19% of the total barometric pressure, further diminishing the oxygen availability.13
休息狀態. 人體的二氧化碳分壓約為 40 mmHg. 二氧化碳也會置換一部分的大氣. 因此. 在海平面. 受到二氧化碳. 水蒸氣. 呼吸道死腔, 等等的影響. 最後肺泡的氧氣分壓約為 100 mmHg. 過度換氣. 會降低血中二氧化碳分壓. 進一步有提升氧分壓的效果(在平地不明顯). 高海拔. 過度換氣現象會比較明顯, 在聖母峰, 吸入的氧氣分壓僅為海平面 29%. 肺泡通氣增加 5 的係數. 極端的過度換氣可將二氧化碳分壓降低至 7-8 mmHg. 僅正常值 1/5 . 因血中二氧化碳的減少. 可提升肺泡內的氧氣. 維持 35mmHg. 足以讓攀登者得以生存.
At rest, the partial pressure of carbon dioxide (PCO2) in the lungs is 40 mmHg, which further displaces oxygen. Although the partial pressure of inspired oxygen at sea-level is 159 mmHg, the combined effects of CO2, water vapor, and dead space reduce the partial pressure of oxygen (PO2) in the lungs to approximately 100 mmHg. Hyperventilation can reduce the partial pressure of CO2 in the lungs below 40 mmHg, thereby allowing the partial pressure of O2 to rise. This effect is exaggerated at altitude. On the summit of Mount Everest where the inspired PO2 is only 29% of its value at sea-level, alveolar ventilation is increased by a factor of 5. This extreme hyperventilation reduces the alveolar PCO2 to 7–8 mmHg, about one-fifth of its normal value. Because of the reduction of PCO2, the alveolar PO2 can rise and be maintained near 35 mmHg, enough to keep the climber alive.14,15
THE HYPOXIC VENTILATORY RESPONSE AND CONTROL OF RESPIRATION
At higher altitudes, the rate and depth of ventilation increase to compensate for the reduced partial pressure of oxygen (PO2). This increase in ventilation is termed the hypoxic ventilatory response (HVR) and is partially mediated by the carotid body which is located at the bifurcation of the common carotid artery and is sensitive to dissolved oxygen in the blood. The primary stimulus to breath, however, is not hypoxia; it is hypercapnia, an increase in the level of carbon dioxide in the blood. This stimulus is mediated by potent chemoreceptors located in the medulla. Although the blood–brain barrier separates these medullary chemoreceptors from the arterial blood, the blood–brain barrier is permeable to CO2. Increases in the arterial pressure of CO2 (PaCO2) and hydrogen ion concentration (acidemia) stimulate respiration, and decreases in PaCO2 and hydrogen ion concentration (alkalemia) depress respiration.
Through the action of carbonic anhydrase, the CO2 generated in peripheral tissues combines with water to form carbonic acid (H2CO3) where it rapidly dissociates into hydrogen and bicarbonate ions as shown below:
The reaction rate of carbonic anhydrase (1) is one of the fastest of all enzymes, and its rate is typically limited by the diffusion rate of the substrates; ionic dissociation (2) is not subject to enzymatic acceleration and is virtually instantaneous. In tissues where there is a high CO2 concentration, the reaction proceeds to the right resulting in increased bicarbonate and hydrogen ion production. The hydrogen ions are buffered by deoxygenated hemoglobin which binds the hydrogen ions and delivers them to the lungs. In the lungs where CO2 is being removed, the binding of oxygen by hemoglobin forces the hydrogen ions off the hemoglobin, and the reaction is reversed.
The serum pH is proportional to the bicarbonate/PaCO2 ratio. Although the PaCO2 depends on the balance between CO2 production and CO2 elimination, it is highly dependent on the rate of CO2 elimination.
Hyperventilation accelerates CO2 elimination and produces a respiratory alkalosis by lowering the PaCO2 and raising the pH of the blood. The decrease in PaCO2 and the resulting alkalosis combine to act on the medullary chemoreceptor to decrease ventilation. Consequently, the ventilatory response to hypoxia, the HVR, becomes especially important in maintaining oxygen saturation, since the normal CO2-mediated ventilatory drive is diminished by the hypocapnia. The magnitude and rapidity of onset of the HVR on arrival at altitude varies considerably from individual to individual, and a failure to increase the HVR contributes to hypoxemia and the development of AMS.17
RENAL ADAPTATIONS TO HIGH-ALTITUDE HYPOXIA
As described in the preceding section, the initial response to high-altitude hypoxia is a respiratory alkalosis produced by hyperventilation. Within minutes, the kidneys respond to the alkalosis with an increased excretion of bicarbonate ions; this renal effect can continue for hours or days and functions to correct the alkalosis and return the pH of the serum toward a normal value.
The kidneys also respond to hypoxia by the secretion of erythropoietin. Erythropoietin leads to an increase in red cell mass and the oxygen-carrying capacity of the blood (dissolved oxygen accounts for only about 2% of the oxygen-carrying capacity); however, it takes several days before an increased rate of erythrocyte production can be measured, and the process is not complete for weeks or months.14,18 For short-term ascents, the erythropoietin-mediated increase in red cell mass is of minor importance, although it is important for extended expeditions. The hematocrit, not the total hemoglobin, is increased during short-term ascents by a reduction in plasma volume caused by a hypoxia-mediated diuresis; the elevation in hematocrit increases the oxygen-carrying capacity per 100 mL of blood.17–20
THE HEMOGLOBIN SATURATION CURVE AT ALTITUDE
When blood is exposed to a high oxygen pressure in the lungs, oxygen rapidly and reversibly combines with hemoglobin to form oxyhemoglobin. At sea-level where the PO2 is approximately 100 mmHg, the arterial oxygen saturation of hemoglobin (SaO2) is 95%–98%. The oxygen–hemoglobin dissociation curve (Figure 2) shows the changes in hemoglobin saturation as the partial pressure of O2 decreases.21 Its sigmoidal shape arises from the fact that the hemoglobin molecule contains four heme groups which each react with a molecule of O2; oxygenation of the first heme group increases the affinity of O2 for the remaining groups. This characteristic shape facilitates oxygen loading in the lungs and oxygen release in the tissues. With increasing altitude, the SaO2 is initially well maintained compared to the PO2 due to the relatively flat component of the upper portion of the oxygen–hemoglobin dissociation curve. As altitude increases, the steeper section of the oxyhemoglobin dissociation curve assumes a greater importance, resulting in a more rapid decrease in SaO2. At 8,400 m on Mount Everest where the partial pressure of arterial oxygen (PaO2) drops to 25 mmHg, hemoglobin saturation is only 50%.
The increased oxygen demands of actively metabolizing tissues lead to an increased production of CO2 and hydrogen ion concentration accompanied by an increase in local temperature and increased levels of 2,3-diphosphoglycerate, all of which shift the oxygen–hemoglobin dissociation curve to the right and facilitate oxygen release in the tissues, while shifts to the left occur under the reverse conditions. At high altitude, the acute respiratory alkalosis arising from hyperventilation causes a leftward shift in the oxygen–hemoglobin dissociation curve, increasing arterial saturation for any given PaO2. This leftward shift improves oxygen uptake in the lungs more than it impairs off-loading in the tissues. Under conditions of extreme hypoxia when pulmonary loading is at a premium, the left-shifted increase in hemoglobin oxygen affinity helps maximize the level of tissue oxygenation for a given difference in oxygen tension between the sites of oxygen loading in the pulmonary capillaries and sites of oxygen unloading in the tissue capillaries.
AMS: CLINICAL FEATURES
The hypoxia of high altitude can lead to sleep disturbances, impaired mental performance, weight loss, and reduced exercise capacity.
SLEEP
Humans rapidly ascending from sea-level to sleep at altitudes above 2,500 m often experience disturbances in sleep quantity and quality caused by a combination of low arterial oxygen levels and periodic breathing. Periodic breathing, oscillations in respiratory frequency and/or tidal volume, is a well documented phenomenon in normal healthy adults.24 Following rapid ascent to high altitude, periodic breathing during sleep is almost universal and contributes to the disturbing dreams, frequent arousals, awakenings, and subjective sense of poor-quality sleep often experienced at altitude.25,26 The underlying pattern of periodic breathing is exacerbated by hypoxia and amplified by an increased hypoxic ventilatory response. The resulting hyperventilation leads to a hypocapnic alkalosis which can depress ventilation even to the point of apnea. Hypoventilation leads to hypoxia and a further reduction in oxygen saturation which, in turn, stimulates hyperventilation and generates a self-sustaining cycle.26 Via its effect on the carotid body, acetazolamide leads to a significant reduction in periodic breathing, improves arterial saturation during sleep at high altitude, and helps to prevent or diminish the symptoms of AMS.26 Because of the risk of respiratory depression, sedative hypnotic drugs should be avoided.
MENTAL PERFORMANCE AND CEREBRAL ATROPHY
The brain normally accounts for 20% of total oxygen consumption. Under the high-altitude conditions of moderate to severe hypoxia, mental performance is impaired.14 Impairment in codification and short-term memory is especially noticeable above 6,000 m, and alterations in accuracy and motor speed occur at lower altitudes.27 Of greater concern are studies that indicate both amateur and professional climbers ascending to very high and extreme altitudes are at risk for subcortical lesions and cortical atrophy.
WEIGHT LOSS AT ALTITUDE
Altitude exposure may lead to considerable weight loss, which appears to be a function of both absolute altitude and the duration of exposure. Physical activity, nausea due to AMS, and lack of palatable food all contribute to weight loss at altitude, and this weight loss can be further exacerbated by gastro-enteritis, upper respiratory infections, and low temperatures. Initial weight losses of approximately 3% occur at elevations below 4,000 m, and weight losses up to 15% may occur during extended stays from 5,000 to 8,000 m.30 The initial weight loss likely reflects a diuresis and loss of water. Beyond this initial diuresis, weight loss appears to be preventable by maintaining physical activity and an adequate dietary intake; unfortunately, some trekking companies skimp on the quality and variety of food and contribute to weight loss by failing to provide an adequate diet. Above 5,000 m weight loss is probably unavoidable and is mainly a result of muscle fiber atrophy independent of activity level, possibly related to the direct effects of hypoxia on protein metabolism
PHYSICAL CONDITION AND EXERCISE
Exercise capacity diminishes with altitude. The alveolar partial pressure of oxygen is slightly higher than the partial pressure of oxygen in the arterial blood, and this alveolar–arterial pressure difference widens progressively during exercise in conjunction with an increased cardiac output, shortened capillary transit time, and greater venous oxygen desideration. At sea-level, this exercise-induced pressure differential is accompanied by a ventilatory response that rises out of proportion to increasing oxygen demands; this heightened ventilatory response is usually sufficient to maintain the arterial PO2 and prevent the development of hypoxemia.32 Under the hypoxic conditions of high altitude, however, the ventilatory response is no longer sufficient to prevent arterial oxygen desaturation with exercise; and even mild arterial desaturation (< 94% SaO2) is associated with a significant reduction in maximum oxygen consumption and endurance performance.33 Maximum oxygen consumption is reduced to about 85% of its value at sea-level at 3,000 m, and it falls to 60% at 5,000 m.14
When combined with rapid ascent, strenuous exercise and over-exertion are risk factors for AMS. In a controlled study of subjects experiencing a simulated altitude gain of 3,000 m in a decompression chamber, exercise significantly reduced arterial saturation (SaO2) and increased the AMS symptom scores.34 The effect of physical conditioning in preventing AMS is more difficult to evaluate since those in good physical condition are apt to engage in more strenuous exercise and undertake more rapid ascent, both risk factors for AMS. Data suggest, however, that subjects in excellent physical condition probably have a risk of AMS similar to that in less highly trained individuals
AMS: RISK FACTORS
AMS is associated with a number of potential risk factors including home elevation, maximum sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, hemoglobin saturation, pre-acclimatization, prior experience at altitude, genetic make-up, and pre-existing diseases.
HOME ELEVATION AND MAXIMUM SLEEPING ALTITUDE
Travelers ascending from sea-level are at higher risk for AMS than those living at higher elevations. This difference is illustrated by a study at a Colorado ski resort showing that the risk of developing AMS was 27% for residents arriving from sea-level compared to 8.4% for those residing above 1,000 m.3 The risk of AMS increases with sleeping altitude; among mountaineers staying at huts in the Swiss Alps, the prevalence of AMS ranged from 9% at 2,850 m to 53% at 4,559 m (Table 2).5 These results are comparable to the prevalence of AMS among trekkers staying at tea houses in Nepal which ranged from 10% at 3,000–4,000 m to 51% at 4,500–5,000 m (Table 2).4 Interestingly, in this study, the prevalence of AMS decreased from 51% at 4,500–5,000 m to 34% above 5,000 m (Table 2) and was likely due to self-selection or prior experience at altitude among those ascending above 5,000 m.
RATE OF ASCENT AND KILIMANJARO
A rapid rate of ascent is an important contributor to the development of AMS.3 Trekkers in the Everest region of Nepal appear to have a slower rate of ascent and a lower prevalence of AMS compared to those climbing Kilimanjaro where the rate of ascent is more rapid.4,6,37,38 In climbers ascending to very high altitudes, differences of a few days in acclimatization can have a significant impact on the prevalence of AMS, symptom severity, and mountaineering success.36
At 5,895 m, Kilimanjaro is the world’s highest free-standing mountain measured from base to summit. It is popular, easily accessible, and its location near the equator offers the option of combining a summit attempt with a safari to neighboring game preserves. Every year 20,000 climbers try to reach the summit.6 The standard routes to the summit, with the possible exception of the Western Breech which requires some scrambling, are not technical and can potentially be hiked by anyone in good physical condition. In spite of the non-technical nature of the climb, there have been numerous fatalities on this mountain.6 To cut costs and compete effectively, trekking companies often schedule relatively rapid climbs leaving limited time for acclimatization. Of particular concern is the observation that some hikers continue to ascend in spite of developing life-threatening signs of high-altitude pulmonary or cerebral edema.6 Although not always practical, current recommendations are to limit the increase in sleeping altitude to 600 m in a 24-hour period once above 2,500 m and to add an extra day of acclimatization for every 600–1,200 m gain in elevation.
LATITUDE
Latitude affects oxygen availability, hemoglobin saturation, and the risk of developing AMS. Due to its rotation, the Earth bulges at the equator; consequently, both barometric pressure and PO2 are higher at the equator than at the poles. On the 6,194 m summit of Denali in central Alaska, the barometric pressure is equivalent to barometric pressure on the summit of a 6,900-m peak in the Himalayas.39 Because of this effect, at an equivalent elevation climbers will be less hypoxic on Kilimanjaro (3°S) or even Everest (23°N) than on Denali (63°N). If Everest had been situated at the same latitude as Denali, it could not have been climbed without supplemental oxygen.
GENDER AND AGE 性別與年齡. 男女性都可能得到AMS. 但某些研究發現女性得到AMS機率稍高. 年紀大的人AMS機率並未更高. 事實上有一篇研究發現. 18-19歲的人. 去科羅拉多滑雪旅館 45% 得到AMS. 60-87歲的人, 僅 16% 得到AMS. 顯然年紀大的這組AMS 機率反而下降. 但這項研究並沒有做到控制. 也許是年輕人運動強度大. 所以得到AMS機率上升. 兒童的臨床研究不多. 但發生率跟成人相似.
Men and women appear to be equally at risk for AMS,4,5,39 although some observational studies suggest a slightly higher risk for women.3 Older individuals do not appear to have an increased risk of AMS;4,36 in fact, one study suggests that younger individuals may be at higher risk. Eighteen-to-nineteen-year-olds had a 45% incidence of AMS at Colorado ski resorts compared to only 16% for those between 60 and 87 years of age.3 This study was uncontrolled, and the results are probably affected by a greater exercise intensity in the younger age group. There are no controlled trials of AMS in children, but the attack rate appears similar to that in adults.40
INTENSITY OF EXERCISE
As described above, the alveolar–arterial pressure difference widens progressively with increasing exercise, leading to reduced hemoglobin saturation at altitude with an increase in the risk and severity of AMS.32,34 To decrease the risk of AMS, strenuous exercise and over-exertion should be avoided immediately after rapid ascent to high altitude.
RTERIAL OXYHEMOGLOBIN SATURATION
Early hypoxemia, a decrease in the SaO2 greater than that expected for a given altitude, is a risk factor for developing AMS.41–43 Early hypoxemia appears to be the result of a diffusion impairment or venous admixture and can be monitored with a pulse oximeter (Figure 3).41–43 Individuals with early hypoxemia should be advised to avoid strenuous exercise and, if continuing to ascend, to ascend slowly. Pulse oximeters are relatively inexpensive and are commonly carried by trekking companies to monitor SaO2 in individuals with worsening symptoms of AMS; however, if they are to be used at very high or extreme altitudes, it is important to check the calibration. SaO2 measurements below 83% may not have the same degree of accuracy and precision as measurements with higher saturations.
Pulse oximeters have a pair of small diodes that emit light of different wavelengths through a translucent part of the patient’s body such as the finger-tip or ear-lobe; based on differences in absorption of the two wavelengths, the instrument can distinguish between deoxyhemoglobin and oxyhemoglobin. To function properly, the pulse oximeter must detect a pulse since it is calibrated to detect the pulsatile expansion and contraction of the arterial blood vessels with the heart-beat. Inaccurate readings may occur in subjects with frost-bite, cold digits, or hypovolemia.
PRIOR AMS AND PREVIOUS EXPOSURE TO ALTITUDE
A prior history of AMS is an important predictor for developing AMS on subsequent exposures to comparable altitudes.45 Conversely, a history of recent or extreme altitude exposure is associated with a lower risk of AMS (6,962 m).45,46 Self-selection is likely an important factor; those who tolerate and enjoy the high mountains without developing AMS are more likely to repeat the experience.
GENETIC ADAPTATIONS
Humans have lived and worked at high altitudes for thousands of years. Perhaps the best known high-altitude populations are the Sherpas and Tibetans in the Himalaya and the Quecha and Ayamara in the Andes. Hemoglobin concentration is higher in the Andean populations than in Himalayan highlanders, whereas Himalayans respond to their hypoxic environment with a higher ventilatory response.47 These differences are likely to have a genetic component, although no specific genetic differences have yet been identified.
Many cellular functions such as protein synthesis are down-regulated by hypoxia, but select subsets are up-regulated. Prominent among the up-regulated subsets is the family of genes governed by hypoxia-inducible factor 1.48 Hypoxia-inducible factor 1 functions as a global regulator of oxygen homeostasis facilitating both O2 delivery and adaptation to O2 deprivation. The first-discovered example of hypoxia-dependent gene expression was erythropoietin which leads to an increased hematocrit and O2-carrying capacity. Another genetic factor which may contribute to high-altitude performance is a polymorphism in the angiotensin-converting enzyme gene that appears to be more prevalent in elite mountaineers and in endurance athletes than in the general population.49 Individuals differ widely in their susceptibility to high-altitude disorders; some suffer the life-threatening complications of high-altitude cerebral or pulmonary edema at altitudes as low as 3,000 m, whereas others can climb to 8,000 m without supplemental oxygen. Genetic influences remain an active area of investigation
PRE-EXISTING DISEASES
Recreational travelers, hikers, and skiers with underlying cardiac or pulmonary diseases often seek advice regarding high-altitude travel. Asymptomatic patients with coronary disease generally do well, although it is probably prudent to avoid highly strenuous exercise; patients with heart failure should avoid the hypoxia of high altitude.51 Severe anemia and sickle cell disease are also contra-indications to high-altitude travel.51 The advice for patients with lung disease depends on the underlying disease, its severity, and the anticipated altitude and activity level; specific recommendations are contained in an extensive review of the subject.
HIGH-ALTITUDE CEREBRAL EDEMA
High-altitude cerebral edema (HACE) is likely a continuum of AMS. AMS is generally self-limiting, whereas HACE can be fatal. Individuals with high Lake Louise scores should be carefully monitored for the signs of ataxia, confusion, and hallucinations which may mark the onset of HACE. HACE is a clinical diagnosis and consists of ataxia and altered consciousness in someone with AMS or high-altitude pulmonary edema. Individuals with AMS should not ascend until symptoms have resolved; if symptoms fail to resolve, they should descend. Individuals with HACE should descend immediately if at all possible and should never descend unaccompanied.
The exact processes leading to high-altitude cerebral edema are unknown although the edema is probably extracellular, due to blood–brain barrier leakage (vasogenic edema), rather than intracellular, due to cellular swelling (cytotoxic edema).53 Vasogenic edema preferentially spreads along white matter tracts, whereas cytotoxic edema affects both gray and white matter. MRI studies of patients with HACE showed that the majority had intense T2 signal in white matter areas, particularly the splenium of the corpus callosum, but no gray matter abnormalities.53 The predilection for the splenium and corpus callosum is puzzling. Possibly the splenium has more easily perturbed cellular fluid mechanics than surrounding tissues. Splenium MRI abnormalities are not limited to patients with HACE and occur in settings that include alcohol use, infections, hypoglycemia, and electrolyte abnormalities;54 in these cases, abnormalities in the splenium were also associated with confusion and ataxia, and this set of symptoms may be characteristic for edema involving the splenium. The cause of death in HACE is brain herniation.
Dexamethasone (see below) can be used to treat AMS and HACE, but, unlike acetazolamide, dexamethasone does not facilitate acclimatization and may give a false sense of security. It is an excellent rescue drug to assist in descent.55,56 If descent is not possible, both oxygen and portable inflatable hyperbaric chambers (Figure 4) improve oxygen saturation and can be effective treatments for subjects with HACE or high-altitude pulmonary edema.
Inflatable hyperbaric chambers are often carried by trekking companies taking clients to altitude; the bags weigh about 6.5 kg and, when expanded, are cylindrical in shape and large enough to accommodate a person (Figure 4). By inflating the bag with a foot pump, the effective altitude can be decreased as much as 1,500 meters (5,000 feet). The foot pump has to be used continuously while the person is in the bag to supply fresh oxygen and to flush out carbon dioxide.
HIGH-ALTITUDE PULMONARY EDEMA
High-altitude pulmonary edema (HAPE) is a potentially fatal consequence of rapid ascent to high altitude. Early diagnosis may be difficult since many of the early symptoms (shortness of breath, tachypnea, tachycardia, reduced arterial saturation, fatigue, and cough) are often present in unaffected climbers at higher altitudes, particularly in cold, dry, or dusty environments. Distinguishing features of high-altitude pulmonary edema include incapacitating fatigue, dyspnea with minimal effort that advances to dyspnea at rest, orthopnea, and a dry non-productive cough progressing to a productive cough with pink frothy sputum due to hemoptysis. Fever may also accompany HAPE, and its presence does not imply infection; prompt administration of antibiotics is not required unless other symptoms or a chest radiograph indicate pneumonia.59
The onset of HAPE is usually delayed and typically occurs 2–4 days after arrival at altitude; it is not uniformly preceded by AMS.14 HAPE is most common at altitudes greater than 3,000 m,52 but HAPE can and does occur at lower altitudes. Over a 7-year period, 47 cases of HAPE were reported at a single Colorado ski resort with an elevation of 2,500 m.60
The pathogenesis of high-altitude pulmonary edema is still a subject for investigation; however, it is probably triggered by an increase in pulmonary artery pressure due to the normal pulmonary vasoconstriction induced by hypoxia. Patients with HAPE have an enhanced pulmonary reactivity to hypoxia, an exaggerated increase in pulmonary artery pressures, and are improved by pharmacological interventions that decrease pulmonary artery pressure.61–63 In a subset of individuals, moderate to intense exercise may play a contributory role since exercise independently leads to an increase in pulmonary artery pressures and this effect may be additive to the increased pressures resulting from hypoxia.
Compelling evidence indicates that HAPE is a hydrostatic-induced permeability leak with mild alveolar hemorrhage.62,64,65 Two explanations have been suggested. The first is that that hypoxic pulmonary vasoconstriction is not homogeneous; consequently, pulmonary capillaries supplied by dilated arterioles are exposed to high pressures which cause damage to the capillary walls (stress failure) and leads to a leak of high-protein edema fluid with erythrocytes.4 The second explanation hypothesizes an increase in pulmonary capillary pressures due to hypoxic pulmonary venous constriction.62,65 Regardless of the mechanisms, successful prophylaxis and treatment of high-altitude pulmonary edema using nifedipine, a pulmonary vasodilator, indicates that pulmonary hypertension is crucial for the development of high-altitude pulmonary edema.63,66
There are no randomized controlled trials evaluating treatment strategies. Oxygen, rest, and descent are commonly agreed upon.59,66 When patients fail to respond to conservative measures or develop HAPE in remote settings, nifedipine is recommended, 10 mg orally initially and then 30 mg of the extended release formulation orally every 12–24 hours.66 Phosphodiesterase inhibitors such as tadalafil have been shown to prevent HAPE in susceptible individuals67 and may also be effective in patient management. Some physicians are now employing combination therapy with nifedipine and phosphodiesterase inhibitors,68 although these are off-label uses. If descent is not possible, use of a portable hyperbaric chamber is recommended.
AMS: PREVENTION AND TREATMENT
Drugs used in the prevention and management of AMS include acetazolamide, dexamethasone, phosphodiesterase inhibitors, and analgesics. Strategies to prevent AMS include preacclimatization, copious water consumption, and a high-carbohydrate diet.
ACETAZOLAMIDE
Acetazolamide is a potent carbonic anhydrase inhibitor; its efficacy in preventing and ameliorating AMS has been well demonstrated although there is still debate regarding the optimal dose.69–71 A recent double-blind, randomized, placebo-controlled study in the Everest region of Nepal showed that 125 mg twice a day was just as effective in preventing AMS as 375 mg twice a day.69 In this study, the incidence of AMS among subjects taking acetazolamide averaged about 22% compared to 51% for those taking a placebo. Acetazolamide is not a panacea; a substantial percentage of subjects taking acetazolamide still develop AMS. In fact, on Kilimanjaro, where the rate of ascent tends to be faster than in Nepal, the incidence of AMS in those taking acetazolamide (250 mg twice a day) was 55% versus 84% for a comparison/placebo group.72 Although the precise dose and recommended duration of treatment have never been established,56 a reasonable approach for prevention is 125 mg twice a day beginning 1 day prior to ascent and continuing for 2 days after reaching maximal altitude or until descent is initiated; if ascent is rapid, 250 mg twice a day may be more efficacious but carries a greater risk of side-effects. In children, the recommended dose of acetazolamide is 2.5 mg/kg orally given every 12 hours with a maximum dose of 250 mg;73 treatment for 48 hours is usually sufficient for resolution of symptoms.40
The actual mechanisms by which acetazolamide increases minute ventilation, leads to improvements in arterial blood gases, and reduces the symptoms of AMS remain poorly understood.71 The efficacy of acetazolamide has been attributed to inhibition of carbonic anhydrase in the kidneys resulting in bicarbonaturia and metabolic acidosis, which offsets the respiratory-induced alkalosis and allows chemoreceptors to respond more fully to hypoxia stimuli at altitude. Other mechanisms, however, are likely involved: the bicarbonaturia ultimately lowers the cerebral spinal fluid (CSF) bicarbonate concentration, thereby lowering the CSF pH and stimulating ventilation.71 Membrane-bound carbonic anhydrase isoenzymes are present on the luminal side of almost all capillary beds including the brain and can be inhibited by low doses of acetazolamide leading to a local tissue retention of CO2 in the order of 1–2 mmHg.71,74 This slight increase in partial pressure of CO2 in the brain may stimulate profound changes in ventilation given the high CO2 ventilatory responsiveness of central chemoreceptors.74 In fact, inhibition of red blood cell and vascular endothelial carbonic anhydrase has been shown to cause an almost immediate retention of CO2 in all tissues as the normal mechanisms for exchange and transport are attenuated. The resulting tissue acidosis is postulated to be an important stimulus to the hyperventilation associated with carbonic anhydrase inhibition.71,74 In addition to improvements in ventilation from tissue acidosis, other operative mechanisms likely include improvements in sleep quality from carotid body carbonic anhydrase inhibition and the effects of diuresis.71
Acetazolamide is a sulfonamide drug; patients with an allergic reaction to sulfonamide antibiotics are more likely to have a subsequent allergic reaction to a non-antibiotic sulfonamide drug, but this association appears to be due to a predisposition to allergic reactions rather than to a specific cross-reactivity with sulfonamide-based antibiotics.75 Nevertheless, the general recommendation is that patients with known allergies to sulfa drugs should avoid acetazolamide.56 The most common side-effects of acetazolamide are peripheral and circumoral paresthesias, but loss of appetite and nausea have been reported. The effect of carbonic anhydrase inhibition in the mouth can also affect the taste of carbonated beverages. Higher doses (250 mg twice or three times a day) are associated with greater side-effects. Finally, the safety of acetazolamide in pregnancy has not been established, and it should be used in pregnancy only if the benefits clearly outweigh the risks.66
DEXAMETHASONE
Dexamethasone is probably less effective than acetazolamide in preventing AMS,70 but it is effective as an emergency treatment of AMS in a dosage of 4–10 mg initially, followed by 4 mg every 6 hours.55,56,76,77 Dexamethasone reduces AMS symptomatology but does not improve objective physiologic abnormalities related to exposure to high altitudes; a subject with severe AMS may have a dramatic response in symptomatology after treatment with dexamethasone but still show cerebral edema on a CT scan.77 At present, dexamethasone is recommended only when descent is impossible or to facilitate co-operation in evacuation efforts.
PHOSPHODIESTERASE INHIBITORS
Decreased nitric oxide synthesis may be a contributory factor in HAPE. Nitric oxide, a vasodilator produced in the pulmonary vascular endothelium, has a short half-life as a result of local phosphodiesterase (PDE) activity; consequently, PDE inhibitors enhance the effect of nitric oxide. The 5-PDE inhibitor sildenafil (Viagra) diminishes the pulmonary hypertension induced by acute exposure to hypobaric hypoxia at rest and after exercise,78 protects against the development of altitude-induced pulmonary hypertension, and improves gas exchange, limiting the altitude-induced hypoxemia and decrease in exercise performance.79 Tadalafil has been shown to prevent HAPE in susceptible individuals,67 and this class of drugs shows promise in the management of patients with HAPE.
ACETAMINOPHEN AND IBUPROFEN
Acetaminophen and non-steroidal anti-inflammatory drugs such as ibuprofen and aspirin are often effective in relieving the headache associated with AMS
HYDRATION
Avoiding dehydration is important, especially since considerable moisture can be lost through respiration at high altitude. Although hypo-hydration degrades aerobic performance at altitude, it does not appear to increase the prevalence or severity of AMS.82 Nevertheless, a belief has developed that hypo-hydration increases the risk of AMS and that excessive hydration can prevent or treat the disorder.83 Some trek leaders even urge clients to consume excess quantities of water to avoid or ameliorate AMS, but there is no scientific basis for this advice.66,84 The belief may have originated from observations on the Jungfraujoch (3,471 m) where it was noted that new arrivals passing the greatest quantity of urine tolerated altitude better than those passing the least amount of urine.83 This observation may have led to the assumption that consuming large quantities of water would lead to a diuresis and prevent AMS. The early diuresis that occurs at altitude, however, is a response to hypoxia not excess fluid consumption; the development of AMS is associated with a rise in the plasma concentrations of antidiuretic hormone and fluid retention
PRE-ACCLIMATIZATION AND ALTITUDE SIMULATION
Pre-acclimatization, spending time at altitude prior to undertaking a higher ascent, reduces the likelihood of developing AMS.46 Living at high elevation and training at low elevation improves performance in athletes of all abilities; the primary mechanism is an increase in erythropoietin which leads directly to an increase in red cell mass. The increase in red cell mass allows greater oxygen delivery to the tissues, an increase in maximum oxygen consumption, and an improvement in exercise capacity.85,86 Pre-acclimatization is usually impractical for the high-altitude traveler or recreational climber, and the “live high, train low” approach is not an option for most athletes. Intermittent hypoxic training has been introduced using normobaric or hypobaric hypoxia in an attempt to reproduce some of the key features of altitude acclimatization and enhance performance.85,87,88 Hypoxia at rest has the primary goal of stimulating acclimatization, while hypoxia during exercise has the goal of enhancing performance.
The simplest intermittent hypoxic training strategy is breathing air with a reduced partial pressure of oxygen under resting conditions; this strategy is straightforward, but unresolved variables are the optimum number of sessions, optimum length of each session, and timing of the sessions prior to ascent. At present, no set of resting, normobaric, hypoxic training parameters have been defined that will reproducibly reduce the likelihood of AMS. A much more sophisticated approach is the use of an altitude simulation system which can safely reduce the oxygen content in a room or tent. This system creates a hypoxic environment that is portable, ideally suited for a “living high, training low” environment and is now used in Olympic training centers around the world.86 Red cell transfusions as well as exogenous erythropoietin have been used to increase red cell mass, but neither approach is legal in athletic competition.
CARBOHYDRATES
Ingestion of pure carbohydrates 40 min prior to acute hypoxic exposure has been shown to improve hemoglobin saturation by as much as 4%; the effect, however, wears off by 150 min, and any advantage of carbohydrate consumption in improving oxygenation is only applicable during the period the carbohydrates are being digested.89 This effect depends on the respiratory quotient (RQ) which represents the ratio of carbon dioxide excreted to the amount of oxygen utilized; the value of this ratio depends on the carbon content of food and is typically around 0.85, but it ranges from 0.7 (pure fat) to 1.0 (pure carbohydrates). As shown in the following equation, metabolism of carbohydrates produces a higher PAO2 than the metabolism of fat:
PAO2 = PiO2 - PaCO2/RQ
where PAO2 is the partial pressure of oxygen in the alveoli, PiO2 is the partial pressure of inspired oxygen, and PaCO2 is the partial pressure of carbon dioxide. A higher PAO2 will result in a higher hemoglobin oxygen saturation. Effectively, the metabolism of carbohydrates produces a larger quantity of CO2 than the metabolism of proteins or lipids;90 the increased CO2 production provides an added stimulus to the respiratory centers.
SUMMARY
The typical symptoms of AMS include headache, loss of appetite, disturbed sleep, nausea, fatigue, and dizziness, beginning shortly after rapid ascent to high altitude. The hypoxia of high altitude can lead to sleep disturbances, impaired mental performance, weight loss, and reduced exercise capacity. Factors impacting the risk of AMS include home elevation, maximum altitude, sleeping altitude, rate of ascent, latitude, intensity of exercise, pre-acclimatization, prior experience at altitude, and genetic make-up. Symptoms can usually be relieved by rest and by delaying further ascent until symptoms have resolved; if symptoms are severe, they can be rapidly relieved by descent to a lower elevation. Acetazolamide in doses of 125 mg twice a day reduces the incidence and severity of AMS in areas of relatively slow ascent such as the Everest region of Nepal; under these conditions, higher doses do not appear to be more effective but may be advantageous during the more rapid ascent that occurs on mountains such as Kilimanjaro. AMS may progress to high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) may occur in the absence of AMS. Both of these conditions are medical emergencies; if possible, initial management should include descent, supplemental oxygen, and, in the case of HACE, dexamethasone. Nifedipine and phosphodiesterase may be effective in the management of HAPE. A person suspected of either of these conditions should never descend alone. Portable hyperbaric chambers should be considered if descent is not an option
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