前天上課時, 有學員說到高海拔肺水腫(HAPE)預防. 提到一個數字. 海拔 4000 公尺. 我又重新看了一次相關文獻. 先整理 uptodate 上面的段落
(下面是我的筆記)
建議的預防方法 —
雖然最初的小型研究結果令人鼓舞，但仍需要進一步研究來確定地塞米鬆或他達拉非等磷酸二酯酶 5 (PDE-5) 抑制劑是否是有效的預防藥物。根據機制和臨床經驗，乙醯唑胺是預防 HAPE 的合理藥物，但缺乏正式研究。對於有明確 HAPE 復發史的高風險個體，沙美特羅只應被視為硝苯地平的輔助預防藥物。
預防藥物 — 提供了用於預防和治療 HAPE 的藥物摘要(表 4 )。以下是對用於預防的藥物的更徹底的討論。
硝苯地平 — 硝苯地平是預防 HAPE 的首選藥物，但僅用於高風險族群且僅在無法適應環境時使用。理想情況下，治療在上升前 24 小時開始，並在目的地海拔持續五天。在風險較高的情況下，治療可能會在目的地海拔持續長達 7 天或直到開始下降。我們每 12 小時給予 30 毫克緩釋製劑。
在一項小型隨機試驗中，當參與者進行陡峭上升時，每 8 小時口服 20 毫克緩釋製劑，可以預防 10 名有胸部X光記錄的反覆發作史的受試者中的 9 名出現 HAPE [ 48 ]。給予安慰劑的 11 名受試者中有 7 名出現了放射線檢查證實的 HAPE。請注意，20 毫克緩釋製劑在美國不可用。
類固醇-地塞米松 — 需要進一步研究以確定地塞米松是否是預防 HAPE 的合適藥物。在一項對29 名有HAPE 病史的個體進行的隨機試驗中，接受地塞米松預防（每12 小時8 毫克）的10 名參與者在從490 公尺快速上升到4559 公尺並過夜期間，沒有一人出現HAPE [ 43 ]。地塞米松預防還具有預防急性高山症/高原腦水腫 (HACE) 的額外優勢，而硝苯地平和 PDE-5 抑制劑則沒有這種作用。
(當身體條件不適合服用丹木斯時, 類固醇可以替代丹木斯, 作為預防AMS/HACE的藥物)
氣管擴張劑(β 受體激動劑) — 在一項小型研究中，沙美特羅預防了 50% 受試者的 HAPE，因此其效果似乎不如其他藥物 [ 52 ]。然而，它是安全的，可以與乙醯唑胺或其他藥物合併使用。選擇沙美特羅進行預防性研究是因為其作用時間相對較長。沙丁胺醇較便宜，可能是有效的預防方法，但這尚未被研究。
1. 放慢每天上升的海拔高度. 還是預防HAPE最主要的方法
2. 當行程無法更動. 必須快速到達高海拔時. 曾發生過HAPE的人. 或者本身罹患肺動脈高壓這個疾病. 才需要考慮預防性服藥
3. 沒發生過HAPE, 沒有罹患肺動脈高壓的一般民眾. 不建議預防性服藥.
HAPE 與AMS 急性高山病的差異. 因 AMS 發生機率極高. 且會影響旅遊品質, 預防性服藥風險不高. 因此建議處於中度至高度風險的遊客/登山客預防性服藥.
HAPE雖然罹病之後危害極大. 但發生率低. 服藥有可能造成風險(血壓過低,暈厥), 多數遊客/登山客並不需要預防性服藥.
4. 關於四千公尺這個海拔. 稍微整理一下文獻上有關敘述
高海拔腦水腫通常發生在海拔 4000 公尺以上(不是肺水腫)
急性肺水腫通常發生在海拔 3000 公尺的二天後, 在海拔2500-3000公尺比較少見。(參考NEJM 2013)
高海拔腦水腫通常發生在海拔 4000 公尺以上(不是肺水腫)
急性肺水腫通常發生在海拔 3000 公尺的二天後, 在海拔2500-3000公尺比較少見。(參考NEJM 2013)
對於不曾發生過HAPE的人. 四天內上升到 4500 公尺（14,800 英尺）的發病率為 0.2%，但在一到兩天內上升時的發病率為 6%。
對於有 HAPE 病史的人來說，在兩天內爬升到 4500 公尺的高度時，復發率為 60%。在 5500 公尺（18,000 英尺）高度，發生率在 2% 到 15% 之間，同樣取決於上升速度。
(下面是參考資料內容)
(這一篇的內容. 在舊的筆記可能也貼過. 就當溫習吧)
流行病學(僅節錄一小段)
HAPE 通常發生在 2500 公尺（8000 英尺）以上，在 3000 公尺（10,000 英尺）以下則不常見（表 1和表 2）[ 8,9 ]。風險取決於個人的敏感度、達到的海拔高度、上升速度以及在高海拔地區停留的時間。對於沒有 HAPE 病史的人來說，在四天內上升到 4500 公尺（14,800 英尺）的發病率為 0.2%，但在一到兩天內上升時的發病率為 6%。對於有 HAPE 病史的人來說，在兩天內爬升到 4500 公尺的高度時，復發率為 60%。在 5500 公尺（18,000 英尺）高度，發生率在 2% 到 15% 之間，同樣取決於上升速度。
HAPE 通常發生在 2500 公尺（8000 英尺）以上，在 3000 公尺（10,000 英尺）以下則不常見（表 1和表 2）[ 8,9 ]。風險取決於個人的敏感度、達到的海拔高度、上升速度以及在高海拔地區停留的時間。對於沒有 HAPE 病史的人來說，在四天內上升到 4500 公尺（14,800 英尺）的發病率為 0.2%，但在一到兩天內上升時的發病率為 6%。對於有 HAPE 病史的人來說，在兩天內爬升到 4500 公尺的高度時，復發率為 60%。在 5500 公尺（18,000 英尺）高度，發生率在 2% 到 15% 之間，同樣取決於上升速度。
HAPE generally occurs above 2500 meters (8000 feet) and is uncommon below 3000 meters (10,000 feet) (table 1 and table 2) [8,9]. The risk depends upon individual susceptibility, altitude attained, rate of ascent, and time spent at high altitude. In those without a history of HAPE, the incidence is 0.2 percent with ascent to 4500 meters (14,800 feet) over four days but 6 percent when ascent occurs over one to two days. In those with a history of HAPE, recurrence is 60 percent with an ascent to 4500 meters over two days. At 5500 meters (18,000 feet), the incidence ranges between 2 and 15 percent, again depending upon rate of ascent.
建議的預防方法 —
逐漸上升仍然是預防包括 HAPE 在內的所有形式的高原疾病的主要方法。對於有 HAPE 病史的人，我們建議睡眠海拔每天的上升速度不超過 400 公尺。對於沒有高山病史或肺動脈高壓病史的患者，HAPE 的風險較低，且不需要常規藥物預防。
對於高風險個體，特別是有 HAPE 病史的個體，藥物預防可能是謹慎的，特別是當時間不允許充分適應時。硝苯地平(降血壓藥物-鈣離子阻斷劑)是預防 HAPE 的首選藥物。如果可能的話，應在上升前一天開始，並在固定高度持續五天，或以漸進的高度增益繼續進行（對於上升速度超過建議速度的人，在達到目的地高度後最多7 天），直到開始下降。
對於高風險個體，特別是有 HAPE 病史的個體，藥物預防可能是謹慎的，特別是當時間不允許充分適應時。硝苯地平(降血壓藥物-鈣離子阻斷劑)是預防 HAPE 的首選藥物。如果可能的話，應在上升前一天開始，並在固定高度持續五天，或以漸進的高度增益繼續進行（對於上升速度超過建議速度的人，在達到目的地高度後最多7 天），直到開始下降。
雖然最初的小型研究結果令人鼓舞，但仍需要進一步研究來確定地塞米鬆或他達拉非等磷酸二酯酶 5 (PDE-5) 抑制劑是否是有效的預防藥物。根據機制和臨床經驗，乙醯唑胺是預防 HAPE 的合理藥物，但缺乏正式研究。對於有明確 HAPE 復發史的高風險個體，沙美特羅只應被視為硝苯地平的輔助預防藥物。
預防藥物 — 提供了用於預防和治療 HAPE 的藥物摘要(表 4 )。以下是對用於預防的藥物的更徹底的討論。
硝苯地平 — 硝苯地平是預防 HAPE 的首選藥物，但僅用於高風險族群且僅在無法適應環境時使用。理想情況下，治療在上升前 24 小時開始，並在目的地海拔持續五天。在風險較高的情況下，治療可能會在目的地海拔持續長達 7 天或直到開始下降。我們每 12 小時給予 30 毫克緩釋製劑。
在一項小型隨機試驗中，當參與者進行陡峭上升時，每 8 小時口服 20 毫克緩釋製劑，可以預防 10 名有胸部X光記錄的反覆發作史的受試者中的 9 名出現 HAPE [ 48 ]。給予安慰劑的 11 名受試者中有 7 名出現了放射線檢查證實的 HAPE。請注意，20 毫克緩釋製劑在美國不可用。
類固醇-地塞米松 — 需要進一步研究以確定地塞米松是否是預防 HAPE 的合適藥物。在一項對29 名有HAPE 病史的個體進行的隨機試驗中，接受地塞米松預防（每12 小時8 毫克）的10 名參與者在從490 公尺快速上升到4559 公尺並過夜期間，沒有一人出現HAPE [ 43 ]。地塞米松預防還具有預防急性高山症/高原腦水腫 (HACE) 的額外優勢，而硝苯地平和 PDE-5 抑制劑則沒有這種作用。
(當身體條件不適合服用丹木斯時, 類固醇可以替代丹木斯, 作為預防AMS/HACE的藥物)
(上面的研究. 使用類固醇的劑量比一般的指引高. 一般指引是建議每12小時 4mg )
地塞米鬆的作用機轉尚不清楚。它可能涉及一氧化氮產生的上調以及肺泡上皮膜鈉通道和鈉鉀 ATP 酶的上調。
犀利士/威而鋼(他達拉非和西地那非) — 在小型研究中，PDE-5抑制劑威而鋼/西地那非和犀利士 他達拉非可預防缺氧性肺動脈高壓和HAPE的發生[ 49-51 ]。最佳劑量尚未確定。威而鋼/-西地那非的治療方案多種多樣，從急性攀登前單劑量 50 或 100 毫克，到在高海拔地區度過 2 至 6 天的個人每天 3 次 40 毫克；我們每八小時給予 50 毫克。對於犀利士-他達拉非，每 12 小時 10 毫克是常用劑量。這些藥物可能比硝苯地平更安全，因為低血壓的風險較小，但它們更昂貴且有嚴重頭痛的風險。威而鋼/西地那非的給藥間隔較短，因為它的半衰期為四到五個小時；他達拉非的半衰期為 17 小時。這些藥物可以在登山當天開始，並在達到最高海拔後持續三到五天；對於上升速度比建議速度快的人，可以延長最多 7 天或直到開始下降。
地塞米鬆的作用機轉尚不清楚。它可能涉及一氧化氮產生的上調以及肺泡上皮膜鈉通道和鈉鉀 ATP 酶的上調。
犀利士/威而鋼(他達拉非和西地那非) — 在小型研究中，PDE-5抑制劑威而鋼/西地那非和犀利士 他達拉非可預防缺氧性肺動脈高壓和HAPE的發生[ 49-51 ]。最佳劑量尚未確定。威而鋼/-西地那非的治療方案多種多樣，從急性攀登前單劑量 50 或 100 毫克，到在高海拔地區度過 2 至 6 天的個人每天 3 次 40 毫克；我們每八小時給予 50 毫克。對於犀利士-他達拉非，每 12 小時 10 毫克是常用劑量。這些藥物可能比硝苯地平更安全，因為低血壓的風險較小，但它們更昂貴且有嚴重頭痛的風險。威而鋼/西地那非的給藥間隔較短，因為它的半衰期為四到五個小時；他達拉非的半衰期為 17 小時。這些藥物可以在登山當天開始，並在達到最高海拔後持續三到五天；對於上升速度比建議速度快的人，可以延長最多 7 天或直到開始下降。
氣管擴張劑(β 受體激動劑) — 在一項小型研究中，沙美特羅預防了 50% 受試者的 HAPE，因此其效果似乎不如其他藥物 [ 52 ]。然而，它是安全的，可以與乙醯唑胺或其他藥物合併使用。選擇沙美特羅進行預防性研究是因為其作用時間相對較長。沙丁胺醇較便宜，可能是有效的預防方法，但這尚未被研究。
(這段是我自己寫的. 在台灣. 多數民眾生活在低海拔地區. 依照臨床經驗, 遇到急性肺水腫的患者. 最常發生的原因是洗腎病患或心臟衰竭的患者. 這類患者使用氣管擴張劑通常無效. 甚至有些患者會越吸越不舒服)
PREVENTION
Suggested approach to prophylaxis — Gradual ascent remains the primary method for preventing all forms of high-altitude illness, including HAPE. For those with a history of HAPE, we recommend an ascent rate of no more than 400 meters per day in sleeping altitude. For patients with no history of medical problems at high altitude or of pulmonary hypertension, the risk of HAPE is low, and routine pharmacologic prophylaxis is not warranted.
In individuals at high risk, particularly those with a history of HAPE, pharmacologic prophylaxis may be prudent, especially when time does not allow for adequate acclimatization. Nifedipine is the drug of choice for prophylaxis against HAPE. It should be started the day prior to ascent if possible and continued for five days at a fixed altitude, or continued with progressive altitude gain (up to seven days after reaching the destination altitude in individuals who ascend faster than recommended) until the start of descent.
While the results of initial small studies are promising, further research is needed to determine whether dexamethasone or phosphodiesterase 5 (PDE-5) inhibitors such as tadalafil are effective prophylactic medications. Based upon mechanism and clinical experience, acetazolamide is a reasonable medication for HAPE prophylaxis, but formal studies are lacking. Salmeterol should be considered only an adjunct prophylactic medication to nifedipine in high-risk individuals with a clear history of recurrent HAPE.
Prophylactic medications — A summary of medications used for the prophylaxis and treatment of HAPE is provided (table 4). More thorough discussions of the drugs used for prophylaxis are found below.
Nifedipine — Nifedipine is the preferred drug for the prevention of HAPE but is used only in high-risk individuals and only when acclimatization is not possible. Ideally, treatment is started 24 hours prior to ascent and continued for five days at the destination altitude. In higher-risk scenarios, treatment may be continued for up to seven days at the destination altitude or until the start of descent. We give 30 mg of the extended-release formulation every 12 hours.
In a small randomized trial, 20 mg of a slow-release formulation taken by mouth every eight hours while the participants performed a steep ascent prevented HAPE in 9 of 10 subjects with a history of repeated episodes documented by chest radiograph [48]. Seven of the 11 subjects given placebo developed radiographically proven HAPE. Note that 20 mg extended-release formulations are not available in the United States.
Dexamethasone — Further study is needed to determine whether dexamethasone is an appropriate medication for prophylaxis against HAPE. In one randomized trial of 29 individuals with a history of HAPE, none of the 10 participants given dexamethasone prophylaxis (8 mg every 12 hours) developed HAPE during a rapid ascent from 490 to 4559 meters with an overnight stay [43]. Prophylaxis with dexamethasone has the added advantage of preventing acute mountain sickness/high-altitude cerebral edema (HACE), whereas nifedipine and the PDE-5 inhibitors have no such effect.
Dexamethasone's mechanism of action remains unclear. It may involve upregulation of nitric oxide production and upregulation of alveolar epithelial membrane sodium channels and sodium-potassium ATPase.
Tadalafil and sildenafil — In small studies, the PDE-5 inhibitors sildenafil and tadalafil prevented hypoxic pulmonary hypertension and the development of HAPE [49-51]. Optimal doses have not been established. Regimens for sildenafil have varied from a single dose of 50 or 100 mg just prior to exposure for acute ascent, to 40 mg three times per day for individuals who spend two to six days at high altitude; we give 50 mg every eight hours. For tadalafil, 10 mg every 12 hours is the usual dose. These drugs are potentially safer than nifedipine because there is less risk of hypotension, but they are more expensive and carry the risk of severe headaches. Sildenafil has shorter dosing intervals because its half-life is four to five hours; tadalafil's half-life is 17 hours. These drugs can be started the day of ascent and continued for three to five days after reaching maximal altitude; they can be extended for up to seven days or until start of descent in individuals who ascend faster than recommended.
Beta agonist — Salmeterol prevented HAPE in 50 percent of subjects in one small study and thus appears less effective than other agents [52]. However, it is safe and can be used in combination with acetazolamide or other medications. Salmeterol was chosen for prophylactic studies because of its relatively longer duration of action. Albuterol is less expensive and may be effective prophylaxis, but this has not been studied.
PREVENTION
Suggested approach to prophylaxis — Gradual ascent remains the primary method for preventing all forms of high-altitude illness, including HAPE. For those with a history of HAPE, we recommend an ascent rate of no more than 400 meters per day in sleeping altitude. For patients with no history of medical problems at high altitude or of pulmonary hypertension, the risk of HAPE is low, and routine pharmacologic prophylaxis is not warranted.
In individuals at high risk, particularly those with a history of HAPE, pharmacologic prophylaxis may be prudent, especially when time does not allow for adequate acclimatization. Nifedipine is the drug of choice for prophylaxis against HAPE. It should be started the day prior to ascent if possible and continued for five days at a fixed altitude, or continued with progressive altitude gain (up to seven days after reaching the destination altitude in individuals who ascend faster than recommended) until the start of descent.
While the results of initial small studies are promising, further research is needed to determine whether dexamethasone or phosphodiesterase 5 (PDE-5) inhibitors such as tadalafil are effective prophylactic medications. Based upon mechanism and clinical experience, acetazolamide is a reasonable medication for HAPE prophylaxis, but formal studies are lacking. Salmeterol should be considered only an adjunct prophylactic medication to nifedipine in high-risk individuals with a clear history of recurrent HAPE.
Prophylactic medications — A summary of medications used for the prophylaxis and treatment of HAPE is provided (table 4). More thorough discussions of the drugs used for prophylaxis are found below.
Nifedipine — Nifedipine is the preferred drug for the prevention of HAPE but is used only in high-risk individuals and only when acclimatization is not possible. Ideally, treatment is started 24 hours prior to ascent and continued for five days at the destination altitude. In higher-risk scenarios, treatment may be continued for up to seven days at the destination altitude or until the start of descent. We give 30 mg of the extended-release formulation every 12 hours.
In a small randomized trial, 20 mg of a slow-release formulation taken by mouth every eight hours while the participants performed a steep ascent prevented HAPE in 9 of 10 subjects with a history of repeated episodes documented by chest radiograph [48]. Seven of the 11 subjects given placebo developed radiographically proven HAPE. Note that 20 mg extended-release formulations are not available in the United States.
Dexamethasone — Further study is needed to determine whether dexamethasone is an appropriate medication for prophylaxis against HAPE. In one randomized trial of 29 individuals with a history of HAPE, none of the 10 participants given dexamethasone prophylaxis (8 mg every 12 hours) developed HAPE during a rapid ascent from 490 to 4559 meters with an overnight stay [43]. Prophylaxis with dexamethasone has the added advantage of preventing acute mountain sickness/high-altitude cerebral edema (HACE), whereas nifedipine and the PDE-5 inhibitors have no such effect.
Dexamethasone's mechanism of action remains unclear. It may involve upregulation of nitric oxide production and upregulation of alveolar epithelial membrane sodium channels and sodium-potassium ATPase.
Tadalafil and sildenafil — In small studies, the PDE-5 inhibitors sildenafil and tadalafil prevented hypoxic pulmonary hypertension and the development of HAPE [49-51]. Optimal doses have not been established. Regimens for sildenafil have varied from a single dose of 50 or 100 mg just prior to exposure for acute ascent, to 40 mg three times per day for individuals who spend two to six days at high altitude; we give 50 mg every eight hours. For tadalafil, 10 mg every 12 hours is the usual dose. These drugs are potentially safer than nifedipine because there is less risk of hypotension, but they are more expensive and carry the risk of severe headaches. Sildenafil has shorter dosing intervals because its half-life is four to five hours; tadalafil's half-life is 17 hours. These drugs can be started the day of ascent and continued for three to five days after reaching maximal altitude; they can be extended for up to seven days or until start of descent in individuals who ascend faster than recommended.
Beta agonist — Salmeterol prevented HAPE in 50 percent of subjects in one small study and thus appears less effective than other agents [52]. However, it is safe and can be used in combination with acetazolamide or other medications. Salmeterol was chosen for prophylactic studies because of its relatively longer duration of action. Albuterol is less expensive and may be effective prophylaxis, but this has not been studied.
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