野外與登山醫學---06-Acute altitude illness WMS 2019 update AMS/HACE prevention Ibuprofen 6 (done)

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update
統一名詞翻譯
AMS 急性高山病
HACE 高海拔腦水腫
acute altitude illness 急性高海拔疾病
NSAID 非類固醇消炎止痛藥
Ibuprofen 布洛芬/芬必得/普羅芬是一種常使用的非類固醇消炎止痛藥, 有兩篇研究顯示每天服用三次 600 mg 布洛芬(一天總量 1800mg)有預防AMS效果 (台灣常見的劑型是 400 mg, 例如 purfen). 第三篇較小規模的研究顯示沒有預防效果.
另一篇研究雖然說有效, 但該研究並無設計對照組, 而是採用該地區以往的AMS發生率作參照

Two trials demonstrated that ibuprofen (600 mg 3 times daily) is more effective than placebo at preventing AMS,42,43 while a third, smaller study showed no benefit.44 Another study claimed to show benefit, but the trial did not include a placebo arm and instead compared the incidence of AMS with ibuprofen with historically reported rates from the region in which the study was conducted.45

目前並無布洛芬與類固醇的療效比較, 有兩篇研究比較布洛芬與丹木斯的差異, 第一篇說, 兩組的高海拔頭痛與AMS發生率相近, 兩篇都顯示, 相較於安慰劑, 布洛芬有預防AMS效果.
Although no studies have compared ibuprofen with dexamethasone, 2 studies have compared ibuprofen with acetazolamide. The first found an equal incidence of high altitude headache and AMS in the acetazolamide and ibuprofen groups, with both showing significant protection compared to placebo.46

一篇更近期的研究顯示, 布洛芬預防AMS效果比丹木斯差,
A more recent trial failed to show that ibuprofen was noninferior to acetazolamide (ie, ibuprofen is inferior to acetazolamide for AMS prophylaxis).47

上面提到的這些研究, 服藥時間較短, 大約 24-48 小時, 因此常時間服用布洛芬, 效益與安全性是否大於副作用, 仍屬未知, 需要更多研究比較丹木斯, 類固醇, 布洛芬的差異. 對於布洛芬是否可用於預防AMS, 目前無法給出明確建議
建議: 對於不想吃(或有禁忌)丹木斯或類固醇的人, 可以服用布洛芬預防AMS, 證據等及 2B

The aforementioned trials all used the medication for a short duration (~24 to 48 h). As a result, efficacy and safety (eg, the risk of gastrointestinal bleeding or renal dysfunction) over longer periods of use at high altitude remain unclear. For these reasons, as well as more extensive clinical experience with acetazolamide and dexamethasone, ibuprofen cannot be recommended over these medications for AMS prevention for rapid ascent. Recommendation. Ibuprofen can be used for AMS prevention in persons who do not wish to take acetazolamide or dexamethasone or have allergies or intolerance to these medications. Recommendation Grade: 2B.

野外與登山醫學----05-Acute altitude illness WMS 2019 update AMS/HACE prevention Ginkgo biloba 5 (done)

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update
統一名詞翻譯
AMS 急性高山病
HACE 高海拔腦水腫
acute altitude illness 急性高海拔疾病

Ginkgo biloba 銀杏萃取物, 有兩篇研究顯示銀杏有預防AMS功效, 但也有其他研究顯示無效, 結果差異或許與銀杏產品的來源及組成有關, 懷孕婦女應避免使用銀杏, 服用抗凝血劑的患者也需小心(可能會增加出血風險),. 對於預防AMS而言, 應該優先考慮使用丹木斯, 不建議使用銀杏萃取物作為預防AMS的方式, 證據等級1C

Although 2 trials demonstrated a benefit of Ginkgo in AMS prevention,35,36 2 other negative trials have also been published.37,38 This discrepancy may result from differences in the source and composition of the Ginkgo products.39 Ginkgo should be avoided in pregnant women40 and used with caution in people taking anticoagulants.41 Acetazolamide is considered far superior for AMS prevention. Recommendation. Ginkgo biloba should not be used for AMS prevention. Recommendation Grade: 1C

野外與登山醫學----03-04-WMS 2019 acute altitude illness update 3 Dexamethasone 類固醇 ~ ~4 Inhaled budesonide 吸入性類固醇

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update

統一名詞翻譯
AMS 急性高山病
HACE 高海拔腦水腫
HAPE 高海拔肺水腫
acute altitude illness 急性高海拔疾病
Acetazolamide 乙醯唑胺, 乙醯偶氮胺, 為方便閱讀記憶, 統一翻譯為丹木斯
Dexamethasone 地塞米松, 一種人工合成的類固醇(腎上腺皮質激素/皮質類固醇), 底下翻譯用類固醇代替 (類固醇還有很多其他不同種類, 藥效及作用時間不太相同)
Inhaled budesonide 一種吸入性類固醇, 布地奈德（Budesonide），常見商品名 Pulmicort，類固醇(腎上腺皮質激素/皮質類固醇), 下面使用吸入性類固醇代替 budesonide

AMS及HACE

Acute mountain sickness and high altitude cerebral edema 

有幾篇回顧性文獻提供AMS和HACE的成因, 臨床表現, 病理生理學. 在臨床觀點, HACE可視為是非常嚴重的AMS, 因此這兩個疾病的預防及治療方式可同時討論,

Information on the epidemiology, clinical presentation, and pathophysiology of AMS and HACE is provided in several extensive reviews. From a clinical standpoint, HACE represents an extremely severe form of AMS; therefore, preventive and treatment measures for the 2 disorders can be addressed simultaneously. 

預防AMS及HACE的方式有下列數種 (依序翻譯)

PREVENTION Measures considered for prevention of AMS and HACE include the following.

1. Gradual ascent 緩慢爬升 建議用以預防AMS及HACE(及HAPE)

2. Acetazolamide 丹木斯
若罹患AMS/HACE為中度或高度風險, 強烈建議使用丹木斯預防
兒童也可以使用丹木斯預防AMS/HACE

3. Dexamethasone 類固醇 罹患AMS為中度或高度風險時, 類固醇可做為丹木斯替代藥物, 證據等級1A
兒童不建議使用類固醇預防AMS/HACE



4. Inhaled budesonide 吸入性類固醇 不建議用吸入性類固醇預防AMS, 證據等級 1C

5. Ginkgo biloba 銀杏萃取物
Although 2 trials demonstrated a benefit of Ginkgo in AMS prevention,35,36 2 other negative trials have also been published.37,38 This discrepancy may result from differences in the source and composition of the Ginkgo products.39 Ginkgo should be avoided in pregnant women40 and used with caution in people taking anticoagulants.41 Acetazolamide is considered far superior for AMS prevention.

Recommendation.
Ginkgo biloba should not be used for AMS prevention.
Recommendation Grade: 1C

Ibuprofen 

Two trials demonstrated that ibuprofen (600 mg 3 times daily) is more effective than placebo at preventing AMS,42,43 while a third, smaller study showed no benefit.44 Another study claimed to show benefit, but the trial did not include a placebo arm and instead compared the incidence of AMS with ibuprofen with historically reported rates from the region in which the study was conducted.45 Although no studies have compared ibuprofen with dexamethasone, 2 studies have compared ibuprofen with acetazolamide. The first found an equal incidence of high altitude headache and AMS in the acetazolamide and ibuprofen groups, with both showing significant protection compared to placebo.46 A more recent trial failed to show that ibuprofen was noninferior to acetazolamide (ie, ibuprofen is inferior to acetazolamide for AMS prophylaxis).47 The aforementioned trials all used the medication for a short duration (~24 to 48 h). As a result, efficacy and safety (eg, the risk of gastrointestinal bleeding or renal dysfunction) over longer periods of use at high altitude remain unclear. For these reasons, as well as more extensive clinical experience with acetazolamide and dexamethasone, ibuprofen cannot be recommended over these medications for AMS prevention for rapid ascent.

Recommendation.
Ibuprofen can be used for AMS prevention in persons who do not wish to take acetazolamide or dexamethasone or have allergies or intolerance to these medications.
Recommendation Grade: 2B.

Acetaminophen 
A single study demonstrated that acetaminophen 1000 mg 3 times daily was as effective as ibuprofen at preventing AMS in trekkers travelling between 4370 and 4940 m in elevation.45 Rather than including a placebo arm, the study attempted to establish the benefit of acetaminophen by comparing the incidence rates in the study with those of untreated trekkers from prior studies that used the same ascent profile. Based on these data, acetaminophen is not recommended for use as a preventive agent over acetazolamide or dexamethasone.

Recommendation.
Acetaminophen should not be used for AMS prevention.
Recommendation Grade: 1C


Staged ascent and preacclimatization 
Two studies showed that spending 6 to 7 d at moderate altitude (~2200 to 3000 m) before proceeding to higher altitude (referred to as “staged ascent”) decreases the risk of AMS, improves ventilation and oxygenation, and blunts the pulmonary artery pressure response after subsequent ascent to 4300 m.16,48 Many travelers to high altitude visit mountain resorts at more moderate elevations between 2500 and 3000 m. The value of short stays at intermediate elevations of ~1500 m for decreasing the risk of AMS during such ascents makes sense from a physiologic standpoint. However, this approach has not been studied in a randomized fashion, aside from 1 cross-sectional study finding a decreased risk of AMS in travelers who spent 1 night at 1600 m before ascent to resort communities between 1920 and 2950 m.5 A larger number of studies examining the effects of repeated exposures to hypobaric or normobaric hypoxia in the days and week preceding high altitude travel (referred to as “preacclimatization”) showed mixed results, with some studies finding benefit in terms of decreased AMS incidence or severity49e51 and others showing no effect.52e55 A significant challenge in interpreting the literature on preacclimatization is the variability among the hypoxic exposure protocols used, as well as the fact that not all studies include evidence that their protocols induced physiologic responses consistent with acclimatization. Implementation of either staged ascent or preacclimatization may be logistically difficult for many high altitude travelers. In general, short-term exposures (eg, 15 to 60 min of exposure to hypoxia, or a few hours of hypoxia a few times before ascent) are unlikely to aid acclimatization, whereas longer exposures (eg, >8 h daily for >7 d) are more likely to yield benefit. Hypobaric hypoxia is more effective than normobaric hypoxia in facilitating preacclimatization and preventing AMS.56 Because the optimal methods for preacclimatization and staged ascent have not been fully determined, the panel recommends consideration of these approaches but does not endorse a particular protocol.

Recommendation.
When feasible, staged ascent and preacclimatization can be considered as a means for AMS prevention. 
Recommendation Grade: 1C

Hypoxic tents
Commercial products are available that allow individuals to sleep or exercise in hypoxic conditions for the purpose of facilitating acclimatization before a trip to high altitude. Only 1 placebo-controlled study has examined their utility.57 Although this study demonstrated a lower incidence of AMS in persons who slept in simulated high altitude conditions compared to normoxia, technical difficulties with the system resulted in a substantial number of study participants not receiving the intended hypoxic dose. Although the systems are marketed to be of benefit and anecdotal reports suggest they are widely used by climbers and other athletes competing at high altitude, there are no data indicating increased likelihood of summit success or improved physical performance. As with the preacclimatization approaches previously described, any benefit that may accrue from these systems is more likely with long hypoxic exposures (>8 h per day) for at least several weeks before planned high altitude travel. Short and/or infrequent exposures, including exercise training, are likely of no benefit. In addition to the cost of the systems and power needed to run them, individuals face the risk of poor sleep, which over a long period of time could have deleterious effects on performance during an expedition.

Recommendation.
Hypoxic tents can be used for facilitating acclimatization and preventing AMS, provided sufficiently long exposures can be undertaken regularly over an appropriate number of weeks and other factors, such as sleep quality, are not compromised.
Recommendation Grade: 2B

Other options
Chewed coca leaves, coca tea, and other coca-derived products are commonly recommended for travelers in the Andes mountains for AMS prevention. Their utility in prevention of altitude illness has not been properly studied, so they should not be substituted for other established preventive measures described in these guidelines.

Multiple studies have sought to determine whether other agents, including antioxidants,58 iron,59 dietary nitrates,60 leukotriene receptor blockers,61,62 phosphodiesterase inhibitors,63 salicylic acid,64 spironolactone,65 and sumatriptan66 can prevent AMS, but the current state of evidence does not support their use.

“Forced” or “over” hydration has never been found to prevent altitude illness and might increase the risk of hyponatremia; however, maintenance of adequate hydration is important because symptoms of dehydration can mimic those of AMS.

Nocturnal expiratory positive airway pressure (EPAP) administered via a single-use nasal strip during sleep is not effective for AMS prophylaxis,67 nor is a regimen of remote ischemic preconditioning.68

No studies have examined short-term oxygen use in the form of either visits to oxygen bars or over-the-counter oxygen delivery systems by which individuals inhale oxygenenriched gas from a small prefilled canister. Due to the small volume of gas (2 to 10 L/canister) and short duration of administration, these interventions are unlikely to be of benefit and, as a result, have no role in AMS/HACE prevention. Other over-the-counter products, such as powdered drink mixes, also lack any evidence of benefit.

野外與登山醫學----01-02--WMS 2019 acute altitude illness update part 1~2

Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update

統一名詞翻譯
AMS 急性高山病
HACE 高海拔腦水腫
HAPE 高海拔肺水腫
acute altitude illness 急性高海拔疾病

簡介及高海拔定義
Introduction 簡介
到海拔 2500 公尺以上地區旅遊, 可能會罹患一種或多種高海拔疾病, 急性高山病AMS, 高海拔肺水腫 HAPE, 高海拔腦水腫 HAPE. 在高海拔地區或探險隊工作的醫師, 可能會遇到一些高海拔疾病的個案, 因此需要熟悉預防性處方以及治療方案.

WMS 召開專家會議, 發展實證醫學為基礎的指引, 以預防或治療高海拔疾病, 提出每一種疾病的預防或治療方式. 根據現有的證據以及利弊考量, 將各種建議分級, 這些建議適用於所有到高海拔活動的旅客, 不管是工作, 休閒, 健行, 滑雪, 或登山.

Travel to elevations above 2500 m is associated with risk of developing 1 or more forms of acute altitude illness: acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). Because large numbers of people travel to such elevations, many clinicians are faced with questions from patients about the best means to prevent these disorders. In addition, clinicians working at facilities in high altitude regions or as members of expeditions traveling to such areas can expect to see persons who are experiencing these illnesses and must be familiar with prophylactic regimens and proper treatment protocols. To provide guidance to clinicians and disseminate knowledge about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute altitude illness. Preventive and therapeutic modalities are presented and recommendations made for each form of acute altitude illness. Recommendations are graded based on the quality of supporting evidence and consideration of benefits and risks/burdens associated with each modality. These recommendations are intended to apply to all travelers to high altitude, whether they are traveling to high altitude for work, recreation, or various activities including hiking, skiing, trekking, and mountaineering.

Defining the threshold for “high altitude” and when to apply these guidelines
高海拔定義, 何時可使用此指引

無法適應高海拔的人, 到達海拔 2500 公尺以上, 有罹患高海拔疾病的風險, 但以前的研究及臨床經驗顯示, 體質敏感的人, 在海拔 2000 公尺以上就有可能罹患 AMS, 甚至HAPE. HACE雖然多數都是在更高的海拔發生, 但也曾有案例在海拔 2500公尺發生 HACE 合併 HAPE.
我們很難界定到底多高的海拔可能發生高海拔疾病, 因為高海拔疾病中, 最常見的 AMS 的症狀並不具特異性, 甚至在幾個研究中, 研究對象在不提升海拔的狀況也符合AMS診斷, 因此在一些分析AMS發生率的研究中, 少許的海拔提升, 就會有一些研究對象被歸類到AMS患者, 而引起其症狀的原因可能不是高海拔, 這種情況會造成AMS發生率被高估, 

Unacclimatized individuals are at risk of high altitude illness when ascending to altitudes above 2500 m. Prior studies and extensive clinical experience, however, suggest that susceptible individuals can develop AMS, and potentially HAPE, at elevations as low as 2000 m. HACE is typically encountered at higher elevations but has also been reported at around 2500 m in patients with concurrent HAPE.7 Part of the difficulty in defining a specific threshold at which altitude illness can develop is the fact that the symptoms and signs of AMS, the most common form of altitude illness, are nonspecific, as demonstrated in several studies in which participants met criteria for the diagnosis of AMS despite no gain in altitude. As a result, studies assessing AMS incidence at modest 不大的 elevations may label individuals as having altitude illness when, in fact, symptoms are related to some other process, thereby falsely elevating the reported incidence of AMS at that elevation. 

因為無法界定一個明確的海拔高度, 專家會議建議預防或治療高海拔疾病時, 不要完全依據海拔高度, 考慮預防策略時, 要根據每個人在以往高海拔地區旅遊的表現. 海拔爬升速率, 高度適應的時間天數

Recognizing the difficulty in defining a clear threshold, the expert panel recommends an approach to preventing and treating acute altitude illness that does not depend strictly on the altitude to which an individual is traveling. Preventive measures should be considered based on the altitude to which the individual is traveling and also account for factors such as history of performance at high altitude, rate of ascent, and availability of acclimatization days (described in greater detail later). 

不要以海拔 2500 公尺以下, 來排除 AMS, HAPE, HACE 診斷. 還需要考慮是否有相符的臨床症狀, 謹慎的排除其他成因, 例如嚴重脫水, 低血鈉, 肺炎, 一氧化碳中毒, 低血糖等等.

Diagnoses of AMS, HAPE, or HACE should not be excluded based on the fact that an ill individual is below 2500 m. These diagnoses should be strongly considered in the presence of compatible clinical features, with careful attempts to exclude other entities such as severe dehydration, hyponatremia, pneumonia, carbon monoxide poisoning, and hypoglycemia.

Acute altitude illness WMS 2019 update AMS/HACE prevention Gradual ascent 1

漸進爬升, 每天爬升的海拔不要太快(通常指睡眠海拔), 對於預防高海拔疾病非常有效. 但以往對於這方面的研究, 通常是回溯性研究(缺點是無法要求實驗組與對照組的身體特質一致性), 只有兩篇是前瞻性研究 (先訂出收案條件以及想評估的項目, 再挑選合適的個案), 睡眠海拔比行進間曾爬升的最高海拔影響更大, 舉例, 第一天從海拔 2500公尺出發, 中間曾經爬升到海拔 3200 公尺, 之後下降到海拔 2900 公尺的營地睡覺, 爬升的海拔要用 2900-2500 公尺來計算, 一天爬升的海拔是 400 公尺, 

漸進爬升是指每天睡眠海拔不要增加太多, 建議以此預防急性高山病 AMS 及 高海拔腦水腫 HACE. 

Gradual ascent
Controlling the rate of ascent, in terms of the number of meters gained per day, is a highly effective means of preventing acute altitude illness; however, aside from 2 recent prospective studies,15,16 this strategy has largely been evaluated retrospectively.17 In planning the rate of ascent, the altitude at which someone sleeps is considered more important than the altitude reached during waking hours.

Recommendation. Gradual ascent, defined as a slow increase in sleeping elevation, is recommended for AMS and HACE prevention. A specific approach is described further later in the text. Recommendation Grade: 1

糖尿病合併慢性腎病何時考慮作腎臟切片

若病人有以下症狀，建議施行腎臟切片，以排除其他造成腎病變之原因：

( 一 ) 未合併糖尿病視網膜病變；

( 二 ) 腎絲球過濾率快速下降； 

( 三 ) 快速增加之蛋白尿或合併腎病症候群；

( 四 ) 頑固型高血壓； 

( 五 ) 多重尿液檢驗異常，如合併小便之紅血球 / 白血球或其柱狀體；

( 六 ) 合併系統性疾病之全身表現

( 七 ) 腎絲球過濾率在使用 ACEi/ARB 後三個月內下降 >30%

糖尿病腎病變惡化危險因子

年齡

糖尿病病史

性別

腎絲球過濾率

血清肌酸酐

尿液白蛋白 - 肌酸酐比值

收縮血壓

糖化血色素

慢性B型肝炎的治療方式及藥物

慢性B型肝炎的治療方式及藥物
chronic hepatitis 

treatment
治療目標:
● 肝發炎指數AST(GOT)、ALT(GPT)恢復正常，避免肝臟持續處於發炎狀態，以免走向肝纖維化、肝硬化、肝癌。
● 血液中測不到B肝病毒量。