高血壓 高尿酸 慢性腎病 胰島素 https://2019medicinenote.blogspot.com/2019/12/blog-post_57.html . 糖尿病相關筆記~目錄 https://2019medicinenote.blogspot.com/2020/01/blog-post_4.html

2026年1月21日 星期三

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.

使用降血脂 statin 預防心血管疾病 JUPITER

2026-01-21 08:29AM
研究名稱縮寫 JUPITER(全文pdf)
使用20mg rosuvastatin 與安慰劑做比較 (台灣常開的劑量是 10mg)
受試者 1萬7802人. 
收納條件 LDL < 130 且 high-sensitivity C-reactive protein ≥2 mg/L. 
實驗終點有好幾種.心肌梗塞、中風、血管重建或死亡
JUPITER試驗的5年NNT為20(95% CI,14至34)。
所有亞組的5年NNT值均低於50。
1. 性別: 男性5年需治療人數(NNT)為17,女性為31;
2. 種族: 白人為21,非白人為19;
3. 肥胖程度: 體重指數≤25 kg/m²者為18,體重指數>25 kg/m²者為21 ;
4. 遺傳: 有冠心病家族史者為9,無冠心病家族史者為26;
5. 有代謝症候群者為19,無代謝症候群者為22;
9. 弗雷明漢風險評分大於10%者為14,弗雷明漢風險評分小於10%者為37。


Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin 
Number Needed to Treat With Rosuvastatin to Prevent First Cardiovascular Events and Death Among Men and Women With Low Low-Density Lipoprotein Cholesterol and Elevated High-Sensitivity C-Reactive Protein: Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)

方法和結果-
利用「他汀類藥物預防應用合理性:一項評估瑞舒伐他汀的干預試驗」(JUPITER)的數據,計算了一系列終點、時間範圍和亞組的絕對風險降低值和相應的需治療人數(NNT)值。 JUPITER是一項隨機對照試驗,評估了瑞舒伐他汀20 mg與安慰劑的療效,受試者為17802名低密度脂蛋白膽固醇<130 mg/dL且高敏C反應蛋白≥2 mg/L的健康男性和女性。此外,也進行了敏感性分析,以探討其他他汀類藥物方案可能對類似一級預防族群產生的影響。

對於心肌梗塞、中風、血管重建或死亡此終點,JUPITER試驗的5年NNT為20(95% CI,14至34)。所有亞組的5年NNT值均低於50。
例如,男性5年需治療人數(NNT)為17,女性為31;
白人為21,非白人為19;
體重指數≤25 kg/m²者為18,體重指數>25 kg/m²者為21 ;
有冠心病家族史者為9,無冠心病家族史者為26;
有代謝症候群者為19,無代謝症候群者為22;
弗雷明漢風險評分大於10%者為14,弗雷明漢風險評分小於10%者為37。

對於包含靜脈血栓栓塞在內的淨血管獲益終點,5年NNT為18(95% CI,13至29)。
對於限制性「硬終點」(心肌梗塞、中風或死亡),5年NNT為29(95% CI,19至56)。

在評估替代藥物理論效用的敏感性分析中,分別針對能達到JUPITER研究中觀察到的相對獲益75%和50%的他汀類藥物方案,估計其5年需治療人數(NNT)值分別為38和57。

所有這些計算結果均優於先前報告的用於高血脂男性一級預防的他汀類藥物(5年NNT為40至70)、抗高血壓治療(5年NNT為80至160)或阿斯匹靈(5年NNT>300)的5年NNT值。
結論—對於高敏 C 反應蛋白升高和低密度脂蛋白膽固醇降低的患者,他汀類藥物治療的絕對風險降低和相應的 NNT 值與已發表的幾種廣泛接受的心血管疾病一級預防干預措施的 NNT 值相當,甚至更優,其中包括對明顯高脂血症患者使用他汀類藥物治療。

The most important action of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is their ability to lower levels of low-density lipoprotein (LDL) cholesterol. Statins have proved highly effective in reducing the risk of cardiovascular events in both primary and secondary prevention studies. However, the magnitude of risk reduction associated with statins is greater than that predicted on the basis of LDL cholesterol lowering alone. A likely explanation for this effect is the antiinflammatory action of statins. Following the observation that high-sensitivity C-reactive protein (hs-CRP) is a powerful predictor of cardiovascular events, investigators in the Cholesterol and Recurrent Events (CARE) and Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) trials demonstrated that the magnitude of risk reduction associated with statin therapy was higher among those with elevated hs-CRP levels. In addition, there is accumulating evidence that statins lower plasma levels of hs-CRP in a manner largely independent of LDL cholesterol lowering. In contrast, little benefit has been demonstrated for statin therapy in the absence of both hyperlipidemia and inflammation. Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a large multinational, long-term, double-blind, placebo-controlled, randomized clinical trial designed to assess directly whether statin therapy (rosuvastatin 20 mg/day) should be given to apparently healthy individuals with low LDL cholesterol levels but elevated hs-CRP levels—a critical issue for the prevention of cardiovascular disease. Support for the concept behind the JUPITER trial is also now available from several recent trials comparing different intensities of statin therapy on disease progression as well as clinical end points. These studies indicate that the hs-CRP level achieved after initiation of statin therapy may be as important as the LDL cholesterol level achieved. All of these data raise the possibility that hs-CRP could be used to target high-risk patients who may benefit from early statin use. Ongoing work will determine whether hs-CRP reduction, independent of LDL cholesterol reduction, results in a net clinical benefit. © 2006 Elsevier Inc. All rights reserved. (Am J Cardiol 2006; 97[suppl]:33A– 41A) 
Numerous avenues of research ranging from basic experimental evidence to population-based observational studies have led to the recognition that cardiovascular disease (CVD) involves a systemic inflammatory process.1 Large epidemiologic studies carried out in diverse populations have repeatedly documented the association between highsensitivity C-reactive protein (hs-CRP), an indicator of inflammation, and CVD outcomes, independent of traditional cardiovascular risk factors.2 However, it remains uncertain whether therapies that lower hs-CRP levels would also result in lower cardiovascular event rates. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most widely studied lipid-lowering agents and the most effective low-density lipoprotein (LDL) cholesterol–lowering medications. Statins lower LDL cholesterol and total cholesterol levels by approximately 20% to 50% and have a lesser effect on lowering triglycerides (10% to 40%) and raising high-density lipoprotein (HDL) cholesterol (5% to 15%) levels. Most studies of the effect of statins on outcomes have shown that for approximately every 1% reduction in LDL cholesterol level, there is an associated 1% reduction in risk of clinical cardiovascular events.3 Data from multiple large-scale randomized clinical trialssupport a similar relative risk reduction with statin therapy for cardiovascular outcomes in both the primary and the secondary prevention of CVD. This has led to the development of current international guidelines that focus on LDL cholesterol lowering as the primary target of therapy, tailoring the level of optimal LDL cholesterol reduction to the individual’s level of cardiovascular risk.3 Several risk prediction models, such as the Framingham risk equations and the European Systematic Coronary Risk Evaluation (SCORE), use traditional risk factors to estimate global CVD risk in asymptomatic individuals.4,5 However, most US women and a large proportion of US men are classified as low risk when the Framingham risk score, as recommended by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, is used to estimate risk in the primary prevention setting. Current US population estimates from the National Health and Nutrition Examination Survey (NHANES) found that 1% of women had high-risk Framingham scores (10-year estimated risk for hard coronary events of 20%) and only 4% of women had intermediate-risk scores (10% to 20%), compared with 5% and 29% in men, respectively.6 Meanwhile, the lifetime risk of developing CVD for both men and women is substantiallyhigher—approximately 1 in 3 for women and 1 in 2 for men

To improve cardiovascular risk stratification and detection, an expert panel assembled by the Centers for Disease Control and Prevention (CDC) and the American Heart Association (AHA) provided a scientific statement on hs-CRP summarizing how it may be applied for clinical cardiovascular risk assessment in primary prevention populations.8 This report termed hs-CRP an independent marker of cardiovascular risk and endorsed its use as part of global risk prediction in asymptomatic individuals, particularly those deemed at intermediate risk for CVD by traditional risk factors.8 The panel also established a set of cut points to be used in clinical practice, with hs-CRP levels of 1 mg/L considered low risk and 3 mg/L, high risk. The Cholesterol And Recurrent Events (CARE) trial first demonstrated that statin therapy also lowers plasma levels of hs-CRP.9 This has since been shown to be a class effect, with an approximate statin-mediated reduction of hs-CRP levels of 20% to 30%.9,10 However, the beneficial value of lowering hs-CRP that is independent of lowering LDL cholesterol is not so clear.
The critical question then becomes whether inflammatory markers, such as hs-CRP, can be clinically useful in selecting patients who may benefit from statin therapy despite having normal LDL cholesterol values. This is the hypothesis driving Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), a long-term, multinational, randomized, double-blind, placebo-controlled study to assess rosuvastatin 20 mg in the primary prevention of cardiovascular events in 15,000 subjects with low LDL cholesterol levels and elevated levels of hs-CRP.


Role of Inflammation in Cardiovascular Disease 
Multiple large-scale prospective studies performed in a variety of populations have demonstrated that hs-CRP is a strong and independent predictor of CVD events, including myocardial infarction (MI), ischemic stroke, sudden cardiac death, and diabetes mellitus.11–22 In the Physicians’ Health Study, an epidemiologic study of 22,000 healthy middleaged men with no clinical evidence of disease, increasing levels of hs-CRP at study entry were associated with up to a 3-fold increase in risk of incident MI and a 2-fold increase in risk of ischemic stroke.12 When directly compared with other novel risk factors—including homocysteine, lipoprotein(a), interleukin-6, intercellular adhesion molecule–1, and serum amyloid A—and standard lipid measures, hsCRP has proved to be the single strongest predictor of cardiovascular risk in apparently healthy women. This is demonstrated in the Women’s Health Study (Figure 1), with a relative risk ratio of 4.4 for the highest versus lowest quartile of hs-CRP.
Moreover, the addition of hs-CRP to traditional cholesterol screening enhanced cardiovascular risk prediction and proved to be independent of LDL cholesterol, suggesting that elevated hs-CRP levels may be particularly useful for identifying asymptomatic individuals who may be at high risk for future cardiovascular events but who have average cholesterol levels. As shown in Figure 2, the poorest eventfree survival in women was among those with high LDL cholesterol and high hs-CRP levels, and the best event-free survival was among those with low LDL cholesterol and low hs-CRP levels. Notably, individuals with low LDL cholesterol levels but high hs-CRP levels were at higher risk than those with high LDL cholesterol levels but low hs-CRP levels. This important finding of higher risk associated with high hs-CRP/low LDL cholesterol is among the motivating factors behind the JUPITER trial because this population of apparently healthy individuals— usually missed by current screening guidelines—is being prospectively studied for the first time.Levels of hs-CRP add important prognostic information on cardiovascular risk not only at all levels of LDL cholesterol but also at all levels of the Framingham risk score (Figure 3). With increasing levels of global coronary risk (Figure 3, left), there was a graded and consistent relation with increasing levels of hs-CRP in a dose-response manner. This additional prognostic information is most clinically relevant for those asymptomatic individuals who are at intermediate risk for CVD based on their traditional risk factor profile (Framingham risk estimate of 5% to 20% for developing coronary artery disease over a 10-year period). Currently, these individuals are not considered eligible for aggressive risk factor modification with statin therapy because their LDL cholesterol levels are below the current therapeutic target of 3.36 mmol/L (130 mg/dL).3 The JUPITER trial was designed to study just this population. The ability of hs-CRP to add prognostic information on global cardiovascular risk after adjustment for all Framingham risk factors has been confirmed in 9 major prospective studies (Figure 4). The hs-CRP marker has also been found to modify the risk associated with the metabolic syndrome, which encompasses a number of proatherogenic, prothrombotic, and proinflammatory risk factors (abdominal obesity, elevated triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose levels).16 This finding may be because of the active role that adipocytes play in inflammatory vascular processes, particularly in central or abdominal tissue. The metabolic syndrome has been associated with increased cardiovascular risk and thus was identified as a target of therapy in NCEP ATP III.3 Individuals with the metabolic syndrome are more likely to have high hs-CRP levels, and those with 1 or 2criteria for the metabolic syndrome have higher hs-CRP levels than those with none. In a study of 14,000 apparently healthy women, median hs-CRP levels for those with 0, 1, 2, 3, 4, or 5 criteria for the metabolic syndrome were 0.68, 1.09, 3.01, 3.88, and 5.75 mg/L, respectively.16 In individuals who met NCEP ATP III criteria for the metabolic syndrome, those with high levels of hs-CRP (3 mg/L) had worse event-free survival than those with low hs-CRP levels (3 mg/L). Figure 5 shows cardiovascular event-free survival in analyses stratified by hs-CRP levels of 1, 1 to 3, and 3 mg/L, which are cutoffs chosen to correspond with CDC recommendations for differentiating low-, intermediate-, and high-risk groups.8 As clearly shown, hs-CRP levels added information at all levels of the metabolic syndrome, just as prior data had demonstrated that hs-CRP added important prognostic information at all levels of LDL cholesterol and at all levels of the Framingham risk score.
Although a number of different markers of inflammation can provide useful information for predicting cardiovascular risk, acute-phase reactant hs-CRP is currently the most accurate marker.23 Inflammatory markers, such as soluble intercellular adhesion molecule–1 and interleukin-6, are not readily measured in clinical settings, partly because of their instability and partly because of measurement error. In contrast, several commercial assays with acceptable coefficients of variation are available for the measurement of CRP, and a program to standardize CRP testing is currently being developed by the CDC.8 Emerging evidence also suggests that hs-CRP may not only be a useful marker of inflammation but may also play an active role in the pathogenesis of atherosclerosis (Figure 6). Specifically, CRP appears to be directly involved in augmenting the innate inflammatory response; inducing prothrombotic factors, such as plasminogen activator inhibitor–1, proinflammatory adhesion molecules, and monocyte chemoattractant protein–1; and interfering with endothelial nitric oxide synthase.24 –27 Recent studies have shown that CRP is produced not only in the liver, as previously believed, but also locally in other tissues, including smooth muscle cells from normal coronary arteries and diseased coronary artery bypass grafts.28,29 Moreover, CRP transgenic mice that were made to overexpress the human CRP gene developed significant thrombosis after arterial damage, suggesting that hs-CRP may be more than just a marker for atherosclerosis.

C-Reactive Protein–Lowering Effects of Statins in Acute Coronary Syndromes 
Until recently, it was not known whether the hs-CRP– lowering action of statins provided any clinical benefit beyond their LDL cholesterol–lowering action. In 2 studies published recently—the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and the Pravastatin or Atorvastatin Evaluation and Infection Therapy– Thrombolysis in Myocardial Infarction 22 (PROVE IT– TIMI 22) studies—the strongest evidence to date is provided for the independent cardiovascular benefits associated with statin-induced hs-CRP lowering.30,31 These 2 trials compared the effects of high-dose atorvastatin with those of low-dose pravastatin, demonstrating that lowering hs-CRP levels through intensive statin therapy reduced progression of coronary plaque and risk of recurrent clinical events in patients with acute coronary syndromes. In PROVE IT–TIMI 22, there was a highly significant relative reduction of CVD events (16%) favoring high-dose statin therapy at a 2.5-year follow-up—although the benefit was seen as early as 30 days from the start of therapy.
A prespecified analysis of PROVE IT–TIMI 22 revealed similar and statistically independent relations between hs-CRP reduction and risk of recurrent coronary events and between LDL cholesterol reduction and risk of such events. When patients were divided into categories on the basis of final hs-CRP and LDL cholesterol levels achieved, those with hs-CRP levels reduced to 2 mg/L had fewer recurrent events, regardless of the LDL cholesterol level achieved by statin therapy. As shown in Figure 7, the patients at highest risk were those in whom both LDL cholesterol and hs-CRP remained elevated despite statin therapy. In patients whose LDL cholesterol was lowered to below study median (1.8 mmol/L [70 mg/dL]) with statin use, those whose hs-CRP levels remained elevated had significantly higher recurrent event rates than those whose CRP levels were reduced to 2 mg/L. Moreover, the correlation between hs-CRP reduction and LDL cholesterol reduction achieved by statin use was small in both trials (correlation coefficient, 0.1 to 0.2). These findings suggest that the beneficial effects of statin therapy for secondary prevention of cardiovascular events may be as much a result of lowering hs-CRP levels as lowering LDL cholesterol levels. REVERSAL demonstrated that lowering hs-CRP levels in patients with coronary disease by intensive statin therapy resulted in reduced atherosclerotic lesion progression; in some patients there was even atheromatous regression, as measured by intravascular ultrasonography (Figure 8). These findings suggest that to maximize the benefit of statin therapy, physicians may need to monitor hs-CRP levels in addition to LDL cholesterol levels for secondary prevention of CVD. JUPITER will clarify whether such monitoring could also be beneficial for primary prevention.


Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) 
Because inflammation is an integral part of the underlying pathophysiology of atherosclerosis and hs-CRP is a useful clinical marker of this inflammatory process, an important unresolved question is whether hs-CRP screening combined with traditional lipid screening would provide an improved strategy for statin use in primary prevention of CVD. The JUPITER trial was designed to answer this question. Several factors governed the design. First, statin therapy has been repeatedly demonstrated to lower the risk of CVD events. Second, several studies have now shown statins to have a greater impact on lowering CVD risk in individuals with higher levels of inflammation.32,33 As already noted, for example, investigators in the CARE trial of secondary prevention found that the benefit of pravastatin was greater among subjects with elevated hs-CRP levels.32 Similarly, in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) of primary prevention with lovastatin, the event reduction among those with low LDL cholesterol but high hs-CRP was virtually identical to that seen in patients with high LDL cholesterol.33 Third, more than half of CVD events occur in individuals with LDL cholesterol levels that current guidelines do not consider eligible for therapy. And finally, because of the hs-CRP–lowering effects of statins, treating individuals with high hs-CRP levels but normal LDL cholesterol levels may extend the benefit of prophylactic statins. The primary objective of the JUPITER trial is to determine whether statin therapy (rosuvastatin 20 mg/ day) will reduce the rate of first major cardiovascular events, defined as the combined primary end point of cardiovascular death, MI, stroke, hospitalization for unstable angina, or arterial revascularization among healthy individuals with low LDL cholesterol levels (3.36 mmol/L [130 mg/dL]) but high hs-CRP levels (2 mg/ L).34 Figure 9 shows the basic JUPITER trial design. Asymptomatic individuals (men aged 55 years, women aged 65 years) who have no prior history of MI, stroke, or myocardial revascularization and who on initial screening are found to have LDL cholesterol levels 3.36 mmol/L (130 mg/dL) and hs-CRP levels 2.0 mg/L are randomized in a double-blind manner to either rosuvastatin 20 mg/day or placebo. All study participants are then observed over a period of 3 to 4 years for the development of a first cardiovascular event. JUPITER has been designed to answer definitively whether those with average or low LDL cholesterol levels but high hs-CRP levels should be treated aggressively with statin therapy to lower their risk of CVD events. Secondary objectives of JUPITER are to evaluate whether rosuvastatin therapy lowers the incidence of type 2 diabetes mellitus, bone fractures, and venous thromboembolism. Given the large sample size and the inclusion of a large number of women and minorities, the study will also provide an important tool for evaluating the safety of longterm rosuvastatin use in various racial and ethnic groups.

Conclusion 
The JUPITER trial is the first large-scale, multinational, double-blind, placebo-controlled clinical trial to investigate the effects of statins in the primary prevention of cardiovascular events in individuals with low levels of LDL cholesterol who may be at risk because of their elevated hs-CRP levels. Trial results could provide an evidence base for the use of hs-CRP in addition to LDL cholesterol to guide statin therapy in primary prevention. Because of its potential impact on public health, this trial represents an extremely important step in understanding the links among inflammation, statin therapy, and CVD prevention— knowledge that could lead to substantial alterations in our approach to cardiovascular prophylaxis and treatment.

Abstract

Background— As recently demonstrated, random allocation to rosuvastatin results in large relative risk reductions for first cardiovascular events among apparently healthy men and women with low levels of low-density lipoprotein cholesterol but elevated levels of high-sensitivity C-reactive protein. However, whether the absolute risk reduction among such individuals justifies wide application of statin therapy in primary prevention is a controversial issue with broad policy and public health implications.
Methods and Results— Absolute risk reductions and consequent number needed to treat (NNT) values were calculated across a range of end points, timeframes, and subgroups using data from Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), a randomized evaluation of rosuvastatin 20 mg versus placebo conducted among 17802 apparently healthy men and women with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L. 
Sensitivity analyses were also performed to address the potential impact that alternative statin regimens might have on a similar primary prevention population. For the end point of myocardial infarction, stroke, revascularization, or death, the 5-year NNT within JUPITER was 20 (95% CI, 14 to 34). All subgroups had 5-year NNT values for this end point below 50; as examples, 5-year NNT values were 17 for men and 31 for women, 21 for whites and 19 for nonwhites, 18 for those with body mass index ≤25 kg/m2 and 21 for those with body mass index greater than 25 kg/m2, 9 and 26 for those with and without a family history of coronary disease, 19 and 22 for those with and without metabolic syndrome, and 14 and 37 for those with estimated Framingham risks greater or less than 10%. For the net vascular benefit end point that additionally included venous thromboembolism, the 5-year NNT was 18 (95% CI, 13 to 29). For the restricted “hard” end point of myocardial infarction, stroke, or death, the 5-year NNT was 29 (95% CI, 19 to 56). In sensitivity analyses addressing the theoretical utility of alternative agents, 5-year NNT values of 38 and 57 were estimated for statin regimens that deliver 75% and 50% of the relative benefit observed in JUPITER, respectively. All of these calculations compare favorably to 5-year NNT values previously reported in primary prevention for the use of statins among hyperlipidemic men (5-year NNT, 40 to 70), for antihypertensive therapy (5-year NNT, 80 to 160), or for aspirin (5-year NNT, >300).
Conclusions— Absolute risk reductions and consequent NNT values associated with statin therapy among those with elevated high-sensitivity C-reactive protein and low low-density lipoprotein cholesterol are comparable if not superior to published NNT values for several widely accepted interventions for primary cardiovascular prevention, including the use of statin therapy among those with overt hyperlipidemia.
Clinical Trial Registration— clinicaltrials.gov. Identifier NCT00239681.

2026年1月19日 星期一

野外與登山醫學 THE 1992 路易斯湖高海拔疾病定義及量化共識會議 LAKE LouisE CoNSENsus ON THE DEFINITION AND QUANTIFICATION OF ALTITUDE ILLNESS

2026-05-25 
CDC 列出的HAPE診斷並未使用 LAKE LouisE CoNSENsus 建議的兩個症狀 + 兩個徵象 

2026-01-20
路易斯湖在位於加拿大落基山脈的班夫國家公園內. 湖面海拔約 1750 公尺. 
症狀 symptoms 是病患覺得自己有哪些不尋常的症狀. 是病患自己說的. 但嬰幼兒或年長者或其他無法清晰明確表達群體. 也可由照護者代為表達病患症狀. 例如全身虛弱. 例如食慾不振. 
徵象 signs 是指身體檢查發現的特定發現. 例如生命體徵(vital signs)體溫.心跳.血壓.氧氣濃度.
要描述紀錄患者的狀況. 除了 symptoms /signs,  還有一些屬於實驗室檢查. 包括抽血,驗尿. 糞便檢查. 各種疾病快篩. 影像學檢查(x光.超音波.電腦斷層. 核磁共振. 心電圖. 肌電圖. 腦波等等等)

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。

The lake louise consensus on the quantification of altitude illness
January 1992-PDF檔案下載處

1991年這次共識會提出HAPE診斷需要有兩個以上的症狀及兩個以上的徵象,

在1991年國際低氧症研討會上,與會者達成共識,對各種高原疾病進行量化。這個過程分為幾個階段,由 Peter Hackett(彼得·哈克特)和Oswald Oelz(奧斯瓦爾德·厄爾茨)主持。
在會議召開前,共識委員會收到了有關高山症定義和量化方法的文件。會議期間,所有代表都有機會參與文件的編寫工作。委員會在會議期間多次召開會議,最後制定了這份共識文件。
本文件反映了截至1991年3月的發展現狀,其內容包括:
a) 高海拔症候群的診斷標準,
b) 對高海拔疾病的各種症狀/徵象進行評分的既定流程。
c) 自我評估問卷,
d) 臨床評估-由觀察者進行

建議在接下來的兩年內,由那些對高原疾病進行實地研究的研究人員使用上述方案,並在 1993 年 2 月 9 日至 13 日於路易斯湖舉行的 1993 年國際缺氧研討會上討論結果

以下診斷標準已被接受。
AMS 急性高山病
在近期海拔升高的情況下,出現頭痛,並伴隨以下至少一種症狀:胃腸道症狀(厭食、噁心或嘔吐)、疲勞或虛弱、頭暈或頭暈、睡眠困難。

HACE
可視為「末期」或重度AMS(急性高山病)。在近期海拔升高的情況下,如果急性高山症患者出現精神狀態改變和/或共濟失調,或非急性高山症患者同時出現精神狀態改變和共濟失調,則應考慮此診斷。


HAPE
在近期海拔升高的情況下,有以下情況:
以下症狀至少出現兩項(症狀是病人自己說的)
靜止時呼吸困難、咳嗽、虛弱或運動能力下降、胸悶或胸悶。
以下徵象至少出現兩項(徵象=身體檢查)
至少有一個肺野出現囉音或喘鳴音、中心性紫紺、呼吸急促、心跳過速。

Campbell 博士評論道:
雖然這並非我的專業領域,但我必須表達一些擔憂,目前提出的所謂分類並非異源性分類。急性高山病(AMS)的定義是基於症狀或綜合徵,而高海拔腦水腫(HACE)的定義則是基於病理生理學。 AMS 的基本病理生理機轉很可能與 HACE 類似。另一方面,HACE 的病理生理機轉也可能導致類似 AMS 的症候群。任何分類(而非簡單的清單)都應盡可能做到同源性分類。
待辦事項:
1)解決 Moran Campbell 對 HACE 定義不明確的擔憂。 
2)Bartsch 建議將呼吸急促和心動過速進行量化。

At the 1991 International Hypoxia Symposium, a consensus process to quantify the various altitude maladies occurred. There were several stages in the process which was chaired by Peter Hackett and Oswald Oelz.
Prior to the conference, a consensus committee was given documents pertaining to definitions and ways to quantify altitude illness. At the conference, all delegates were given the opportunity to have input into the preparation of the document. The committee met on several occasions during the meeting and developed this consensus document.
This document represents the present state of its evolution, as of March, 1991. It consists of:
a) diagnostic criteria of altitude syndromes,
b) an agreed process of scoring the various symptoms/signs of altitude illness.
c) self assessment questionnaires,
d) clinical assessment-performed by an observer

It is proposed that the above schema be used over the next two years by those investigators conducting field research into altitude illness and the outcome discussed at the 1993 International Hypoxia Symposium at Lake Louise, February 9-13, 1993.

The following DIAGNOSTIC CRITERIA were accepted
AMS
In the setting of a recent gain in altitude, the presence of headache and at least one of the following symptoms: gastrointestinal (anorexia, nausea or vomiting), fatigue or weakness, dizziness or lightheadedness, difficulty sleeping.

HACE
Can be considered "end stage" or severe AMS. In the setting of a recent gain in altitude, the presence of a change in mental status and/or ataxia in a person with AMS, or the presence of both mental status change and ataxia in a person without AMS.

HAPE

In the setting of a recent gain in altitude, the presence of the following:
Symptoms: at least two of:
dyspnea at rest, cough, weakness or decreased exercise performance, chest tightness or congestion.
Signs: at least two of:
rales or wheezing in at least one lung field, central cyanosis, tachypnea, tachycardia.

Comment from Dr. E.J.M. Campbell:
Although this is not my field, I must express some concern that the so-called classification put forward is not heterologous. AMS is defined in symptomatic or syndromal terms whereas HACE is defined in pathophysiological terms. It may well be that AMS has as its basic pathophysiology something not unlike HACE. On the other hand, it may well be that the pathophysiology ofHACE can cause a syndrome like AMS. It is much preferable that any classification (as opposed to simply a list) should be isologous. To be done: 1) Address Moran Campbell's concern about unclear definition of HACE. 2. Bartsch suggests that tachypnea and tachycardia should be quantified.

Emergency treatment of anaphylaxis 英國--全身性嚴重過敏治療指引

2026-01-20 相關筆記連結
1. anaphylaxis 嚴重全身性過敏反應 治療藥物與頻次劑量
2. 野外與登山醫學---對磺胺類藥物過敏的人可否服用丹木斯
3. anaphylaxis 全身性嚴重過敏反應 腎上腺素劑量
4. 名詞翻譯~ Anaphylaxis 全身性嚴重過敏反應
5. anaphylaxis 全身性嚴重過敏反應 診斷標準與治療
6. 野外與登山醫學-epipen 腎上腺素筆-全身性嚴重過敏反應治療用藥
7. 全身性嚴重過敏反應-Fatal anaphylaxis 死亡案例接觸過敏原之後出現症狀的時間 from uptodate

這篇是 (May 2021 英國)全身性嚴重過敏反應治療指引 

重點建議
1. 全身性嚴重過敏反應是會危及生命的過敏反應
2. 辨識是否為全身性嚴重過敏反應可依據
    a. 突然快速的症狀進展
    b. 會出現呼吸道, 呼吸, 或循環問題
    c. 皮膚或黏膜異常, 潮紅, 蕁麻疹, 血管性水腫, 有20%個案不會出現這些
當個案暴露於已知的過敏原之後出現以上症狀, 可能是全身性嚴重過敏反應
可以參照 ABCDE步驟處理危及生命的問題
Airway, Breathing, Circulation, Disability, Exposure (ABCDE) 
當ABC出現問題, 第一線治療藥物是腎上腺素, 以肌肉注射方式施打在大腿前外側
若施打一次的五分鐘內沒反應., 可施打第二次


Key recommendations for clinical practice
• Anaphylaxis is a potentially life-threatening allergic reaction. 

• Recognise anaphylaxis based on: 
1. sudden onset and rapid progression of symptoms 
2. Airway and/or Breathing and/or Circulation problems 
3. skin and/or mucosal changes (flushing, urticaria, angioedema) – but these may be absent in up to 20% of cases. 
The diagnosis is supported if a patient has been exposed to an allergen known to affect them.

• Treat life-threatening features, using the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. 

Adrenaline is the first-line treatment for anaphylaxis. Give intramuscular (IM) adrenaline early (in the anterolateral thigh) for Airway/Breathing/Circulation problems. 
*** A single dose of IM adrenaline is well-tolerated and poses minimal risk to an individual having an allergic reaction. If in doubt, give IM adrenaline. 
*** Repeat IM adrenaline after 5 minutes if Airway/Breathing/Circulation problems persist. 

• Intravenous (IV) adrenaline must be used only in certain specialist settings, and only by those skilled and experienced in its use.
*** IV adrenaline infusions form the basis of treatment for refractory anaphylaxis: seek expert help early in patients whose respiratory and/or cardiovascular problems persist despite 2 doses of IM adrenaline. 

• Follow the National Institute for Health and Care Excellence (NICE) guideline for the assessment and referral of patients suspected to have had anaphylaxis. Specifically:
*** All patients should be referred to a specialist clinic for allergy assessment.
*** Offer patients (or, if appropriate, their parent and/or carer) an appropriate adrenaline injector as an interim measure before the specialist allergy assessment (unless the reaction was druginduced).
*** Patients prescribed adrenaline auto-injectors (and/or their parents/carers) must receive training in their use, and have an emergency management or action plan 

• Further research is needed to better identify and treat patients at greatest risk of severe anaphylaxis.
*** Anaphylaxis reactions should be reported to the UK Anaphylaxis Registry at www.anaphylaxie.net (to register, email anaphylaxis.registry@ic.ac.uk).
*** Follow guidance for reporting and debriefing of adverse events.

Summary of changes from previous guideline
This guideline replaces the previous guideline from Resuscitation Council UK (RCUK): Emergency treatment of anaphylactic reactions – Guidelines for healthcare providers (originally published January 2008, annotated July 2012 with links to NICE guidance).
• Greater emphasis on intramuscular adrenaline to treat anaphylaxis, and repeated after 5 minutes if Airway/Breathing/Circulation problems persist. 
• A specific dose of adrenaline is now included for children below 6 months of age. 
• Increased emphasis on the importance of avoiding sudden changes in posture and maintaining a supine position (or semi-recumbent position if that makes breathing easier for the patient) during treatment. 
• There are 2 algorithms:
*** Initial treatment of anaphylaxis, with emphasis on repeating the dose of adrenaline after 5 minutes and giving an IV fluid bolus if Airway/Breathing/Circulation problems persist.
*** Treatment of refractory anaphylaxis, defined as anaphylaxis where there is no improvement in respiratory or cardiovascular symptoms despite two appropriate doses of IM adrenaline.

• IV fluids are recommended for refractory anaphylaxis, and must be given early if hypotension or shock is present. 
• Antihistamines are considered a third-line intervention and should not be used to treat Airway/Breathing/Circulation problems during initial emergency treatment.  
*** Non-sedating oral antihistamines, in preference to chlorphenamine, may be given following initial stabilisation especially in patients with persisting skin symptoms (urticaria and/or angioedema).

• Corticosteroids (e.g. hydrocortisone) are no longer advised for the routine emergency treatment of anaphylaxis. 
• New guidance is offered relating to the duration of observation following anaphylaxis, and timing of discharge.

1. Introduction
1.1 Purpose of this guideline 
Increasing numbers of people are presenting to UK hospitals with anaphylaxis. 4,5 Despite previous guidelines, at least 50% of reactions are not treated with IM adrenaline (the firstline treatment of anaphylaxis)6 and treatment, investigation and follow-up of patients with anaphylaxis is suboptimal.
This guideline replaces the previous guideline from Resuscitation Council UK: Emergency treatment of anaphylactic reactions – Guidelines for healthcare providers (originally published January 2008, annotated July 2012 with links to NICE guidance).1 There are no randomised controlled clinical trials in humans providing unequivocal evidence for the optimal treatment of anaphylaxis; such evidence is unlikely to be forthcoming.11,12 Nonetheless, the evidence-base for specific management strategies has increased, and international guidelines have been updated.
This guideline provides:
• an updated consensus about the recognition and treatment of anaphylaxis in all healthcare settings 
• a focus on the treatments that patients with anaphylaxis should receive, that are relevant to all healthcare providers 
• recommendations for treatment that are easy to implement, and that will be appropriate for most anaphylaxis reactions 
• new guidance on the treatment of refractory anaphylaxis. 

This guideline does not cover every possible anaphylaxis scenario, and has been written to be as simple as possible to facilitate teaching, learning and implementation. Improved implementation should reduce harm and deaths from anaphylaxis.

1.2 略

1.3 Key points 
Treatment of anaphylaxis should be based on general life-support principles:
• Call for help early. 
• Use the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach to recognise and treat problems. Treat the greatest threat to life first. 
• Give IM adrenaline to treat Airway/Breathing/Circulation problems. 
• Initial treatment should not be delayed by a lack of a complete history or definite diagnosis. 
• Repeat IM adrenaline after 5 minutes if features of anaphylaxis do not resolve.

Patients having anaphylaxis in any setting should expect the following as a minimum: 
• recognition that they are seriously unwell 
• an early call for help (resuscitation team or ambulance) 
• initial assessment and treatment based on an ABCDE approach 
• prompt treatment with IM adrenaline 
• investigation and specialist follow-up in an allergy clinic. 

Both IM and IV routes are recommended for the treatment of anaphylaxis in the perioperative setting. IV adrenaline should be used for anaphylaxis only by experienced specialists in an appropriate setting (e.g. critical care and peri-operative settings). See Section 5.1.2 for more information.

1.4略

2. Anaphylaxis
2.1 Definition of anaphylaxis 
The World Allergy Organisation Anaphylaxis Committee defines anaphylaxis as: 11
 "A serious systemic hypersensitivity reaction that is usually rapid in onset and may cause death. Severe anaphylaxis is characterized by potentially life-threatening compromise in airway, breathing and/or the circulation, and may occur without typical skin features or circulatory shock being present.” 

Anaphylaxis is a clinical diagnosis; a precise definition is not important for treatment.

Anaphylaxis is characterised by: 
• Sudden onset and rapid progression of symptoms. 
• Airway and/or Breathing and/or Circulation problems. 
• Usually, skin and/or mucosal changes (flushing, urticaria, angioedema).

 The diagnosis is supported if a patient has been exposed to an allergen known to affect them. However, in up to 30% of cases there may be no obvious trigger. Remember: 
• Skin or mucosal changes alone are not a sign of anaphylaxis. 
• Skin and mucosal changes can be subtle or absent in 10–20% of reactions (e.g. some patients present initially with only bronchospasm or hypotension).

Gastrointestinal symptoms (e.g. nausea, abdominal pain, vomiting) in the absence of Airway and/or Breathing and/or Circulation problems do not usually indicate anaphylaxis. Abdominal pain and vomiting can be symptoms of anaphylaxis due to an insect sting or bite. 
Anaphylaxis lies along a spectrum of severity in terms of allergic symptoms.11 (Figure 1)

2.2略

2.3 Pathophysiology of anaphylaxis 
In anaphylaxis, the activation of multiple inflammatory pathways causes Airway/Breathing/ Circulation problems: 
• Tissue oedema and smooth muscle contraction in the airways (causing bronchospasm and wheeze). This is the most common presentation for food-induced anaphylaxis. 
• Fluid extravasation (tissue oedema, hypovolaemia), and a profound reduction in venous tone.28,29 
*** If severe, this mix of hypovolaemic and distributive shock cannot be overcome by compensatory mechanisms and combine to cause reduced blood flow back to the heart and an underfilled ventricles. 29 
• Depressed myocardial function has also been reported, which can cause cardiogenic shock. Electrocardiographic changes have been noted. Release of mediators may cause arrhythmia such as supraventricular tachycardia; a reduction in coronary perfusion may cause or contribute to ST-segment or T-wave changes.29 
• Fluid leakage into the bowel and smooth muscle contraction (resulting in abdominal and pelvic cramps).

In a landmark paper, Fisher described 205 adult patients with peri-operative anaphylaxis, many of whom had central venous monitoring in place. 31 He reported: 
• low right-heart filling pressures in all patients without cardiac disease; despite having elevated pressures, 9 of 11 patients with cardiac disease appeared to need volume expansion to achieve a stable blood pressure 
• increases in haematocrit in 22 patients were indicative of extravasation of up to 35% of circulating blood volume within 10 minutes of reaction onset. 

These data emphasise the need for aggressive fluid resuscitation in anaphylactic shock. 

Changes in posture from supine to standing or sitting upright have been associated with cardiovascular collapse and death during anaphylaxis.32,33 The change in posture further reduces venous return to the heart; this can lead to a further reduction in cardiac output and can compromise myocardial perfusion. 
Keeping a patient with cardiovascular instability flat, with or without the legs raised, will maximise venous return to the heart and is therefore a key component of the initial response to anaphylaxis (see section 4.3). Patients with predominantly respiratory symptoms (and no evidence of cardiovascular instability) may prefer to be in a semi-recumbent position. Pregnant patients should lie on their left side to prevent aortocaval compression, if necessary, with the bed in a head-down position (see Section 4.7).

3. Recognition of anaphylaxis
Look for: 
• Sudden onset of Airway and/or Breathing and/or Circulation problems. 
• Usually, skin and/or mucosal changes (flushing, urticaria, angioedema).

Skin or mucosal changes alone are not a sign of anaphylaxis and may be absent in up to 20% of reactions.
Confusion may arise because some patients have systemic reactions that are not anaphylaxis. Generalised urticaria, angioedema, and rhinitis are not considered to be anaphylaxis because life-threatening features – an Airway and/or Breathing and/or Circulation problem – are not present. However, if in doubt, give IM adrenaline and seek expert help. 
Most reactions develop quickly over minutes: the timing is dependent on the trigger (see Table 2 and Figure 4). Allergens given by a parenteral route (e.g. IV drug, intramuscular injection, insect sting) cause a more rapid onset of symptoms than reactions to an ingested food or drug.
Different symptoms are often associated with different triggers, as shown in Table 2. Most anaphylaxis in children is due to food, which may explain why respiratory presentations of anaphylaxis are more common in this age group. In around 5 -10% cases, no obvious trigger can be identified. 

3.2 Airway / Breathing / Circulation problems 
Patients can have either an A or B or C problem, or any combination. Use the ABCDE approach to recognise these and treat early.

Airway problems
Airway swelling (throat and tongue swelling causing difficulty in breathing/swallowing; patients may feel their throat is closing) 
• Hoarse voice 
• Stridor (a high-pitched inspiratory noise caused by upper airway obstruction)

Breathing problems
• Increased work of breathing 
• Bronchospasm (wheeze) and/or persistent cough 
• Patient becoming tired with the effort of breathing (fatigue) 
• Hypoxaemia (SpO 2 <94%) which may cause confusion and/or central cyanosis 
• Respiratory arrest

Circulation problems
• Signs of shock: o pale, clammy o significant tachycardia (increased heart rate) o hypotension (low blood pressure) 
• Dizziness, decreased conscious level or loss of consciousness 
• Arrhythmia 
• Cardiac arrest

Breathing problems can vary from mild bronchospasm to life-threatening asthma with no other features to suggest anaphylaxis.42 Anaphylaxis can present primarily as respiratory arrest.19,22,27 Consider anaphylaxis in a person with sudden onset breathing difficulties, especially if known to be allergic to a food or insect sting. 

Circulation problems (often referred to as anaphylactic shock) can be caused by vasodilation, by capillary leak with loss of fluid from the circulation, and by direct myocardial depression (see Figure 5). Characteristically, these cause a compensatory tachycardia.20,29 Bradycardia (a slow heart rate) is usually a late feature, often preceding cardiac arrest, 29 but has also been reported in insect/venom anaphylaxis, occurring with the onset of hypotension.44 

Anaphylaxis can also cause myocardial ischaemia and electrocardiogram (ECG) changes,31 even in individuals with normal coronary arteries.43 Anaphylaxis can also affect a patient’s neurological status (Disability problems) because of decreased brain perfusion or the effect of local allergic mediators in the central nervous system. There may be confusion, agitation and loss of consciousness. Patients are usually anxious and may experience a “sense of impending doom”.45 Patients may also have gastrointestinal symptoms (abdominal pain, incontinence, vomiting). These symptoms are more likely to indicate anaphylaxis in the context of reactions due to insect bite or sting, snake bite or parenteral administration of drugs.

3.3 Skin and/or mucosal changes
These are assessed as part of the Exposure when using the ABCDE approach. 
• These are often the first feature of allergic reactions and are present in over 80% of anaphylaxis.37 
• They can be subtle (e.g. patchy erythema) or dramatic (generalised rash). 
• They may involve the skin, the mucosal membranes (e.g. lips), or both. 
• There may be urticaria (also called hives, nettle rash, weals or welts), which can appear anywhere on the body. Weals may be pale, pink or red, can be different shapes and sizes, and are often surrounded by a red flare. They are usually itchy. 
• Angioedema involves swelling of deeper tissues, most commonly in the eyelids and lips, and sometimes the tongue and in the throat. 

Although skin changes can be worrying or distressing for patients and those treating them, skin changes without life-threatening Airway/Breathing/Circulation problems are not anaphylaxis. Reassuringly, most patients who present with skin changes caused by an allergic reaction do not go on to develop anaphylaxis.

3.4 Differential diagnosis 
• Following an ABCDE approach will help with treating the differential diagnoses. 
• In all of the circumstances below, IM adrenaline is unlikely to cause harm and might be clinically useful. 

Life-threatening conditions: 
• Sometimes anaphylaxis can present with symptoms and signs that are very similar to life-threatening asthma – this is most common in children. • Hypotension is a late sign in children. • Seek expert help early if there are any doubts about the diagnosis and treatment. 
Other conditions which can mimic anaphylaxis (but do not respond to adrenaline): 
• inducible laryngeal obstruction (ILO, formerly known as vocal cord dysfunction) 
• ACE inhibitor-induced angioedema, which can be life-threatening and typically does not respond to adrenaline.

Non-life-threatening conditions (these usually respond to simple measures): 
• faint (vasovagal episode) – this can occur in the context of non-anaphylaxis allergic reactions (see below) 
• panic attack 
• breath-holding episode in a child 
• spontaneous (non-allergic) urticaria or angioedema. 

There may be difficulty distinguishing between anaphylaxis and a panic attack. Patients with prior anaphylaxis may be prone to panic attacks if they think they have been re-exposed to the allergen that caused a previous reaction. The sense of impending doom and breathlessness leading to hyperventilation are symptoms that can resemble anaphylaxis. Sometimes, there may be flushing, or blotchy skin associated with anxiety adding to the diagnostic difficulty. 

Diagnostic difficulty may also occur with vasovagal attacks after immunisation or other procedures, but the absence of rash, breathing difficulties, and swelling are useful distinguishing features, as is the slow heart rate in a vasovagal attack (whereas anaphylaxis is usually associated with a tachycardia). Symptoms should resolve rapidly on lying flat. If rapid recovery does not happen, consider anaphylaxis as a cause.

下圖. 如何鑑別迷走神經反射造成暈厥或全身性嚴重過敏反應

























頑固性全身性嚴重過敏反應
多數全身性嚴重過敏反應打一次腎上腺素就會改善. 10% 需打第二劑才有反應. 2.2% 需要施打超過兩次才有反應
4.8 Refractory anaphylaxis 
Most of the anaphylaxis reactions occurring in a community setting will respond to initial treatment with IM adrenaline, although currently around 10% receive a second dose and 2.2% (95% confidence interval, 1.1- 4.1%) receive more than two doses. 6
All healthcare professionals should be able to identify patients with Breathing and/or Circulation problems of anaphylaxis which do not respond to initial treatment with IM adrenaline, and to escalate care quickly by calling for support from the resuscitation team or from the ambulance service for urgent transfer to hospital.







2026年1月14日 星期三

完整接種肺炎鏈球菌疫苗 (Pneumococcal Vaccine)之後不需要再接種疫苗

2026-01-15 09:56AM


下列情況代表已完整接種肺炎鏈球菌疫苗, 已達保護效益(之後不需再接種疫苗)
1. 接種一次 PCV20即達到完整接種肺炎鏈球菌疫苗
2. 曾接種 PCV 13 間隔至少一年再接種 PCV 23
3. 曾接種 PCV 15 間隔至少一年再接種 PCV 23
4. 曾接種 PCV 23 間隔至少一年再接種 PCV 20
5. 曾接種 PCV 13 間隔至少一年再接種 PCV 20
6. 曾接種 PCV 15 間隔至少一年再接種 PCV 20
(目前尚有PCV23價疫苗. 等23價用罄. 之後會以 PCV20 取代)
7. 特殊族群: 侵襲性肺炎鏈球菌感染症IPD高風險對象. 雖已經完整接種. 但可在前劑滿五年後再次接種 PCV20(追加劑)

** IPD 高風險對象: 脾臟功能缺損. 先天或後天免疫不全. 人工耳植入. 腦脊髓液滲漏. 一年內接受免疫抑制劑或放射治療治療的惡性腫瘤者. 器官移植者
** 完成基礎劑之後. 有些人無法產生足夠抗體. 在基礎劑完成之後28天再接種一劑"基礎追加劑"
** 完成基礎劑之後. 雖已經產生抗體. 但隨時間流逝. 抗體濃度逐漸下降. 接種追加劑以提高抗體濃度. 

疾管署-肺炎鏈球菌疫苗專區
從未接種過13或15價結合型肺炎鏈球菌疫苗(PCV13/15)或PCV20及PPV23者,接種1劑PCV20。
曾經接種肺炎鏈球菌疫苗者,依下列原則接種:
(1) 僅曾接種 PPV23 且間隔至少 1 年者,接種 1 劑 PCV20。
(2) 僅曾接種 PCV13/15 且間隔至少 1 年者
(IPD 高風險對象或 65 歲以上「機構住民」及「洗腎患者」間隔至少 8 週),以 1 劑 PPV23銜接接種。如已接種過 PCV13/15 及 PPV23 或 PCV20,代表已完整接種肺炎鏈球菌疫苗,無需再接種 PCV20*。


Q10:如已接種PCV13/15及PPV23或已接種PCV20,可否再公費接種肺炎鏈球菌疫苗?

A:依接種原則,已接種PCV13/15及PPV23或已接種PCV20者,即已完整接種達保護效益,無需再接種PPV23及PCV20。惟若已自費完成接種PCV13/15及PPV23或接種PCV20者,民眾仍有公費接種PCV20需求,間隔至少5年,經醫師評估可公費提供1劑PCV20。

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