野外與登山醫學 丹木斯Acetazolamide是否能預防高海拔肺水腫 HAPE?

2023-10-07 11:47AM
答案: 目前醫學證據顯示, 丹木斯可用於預防再返性 re-entry HAPE.
但不建議用於預防一般的 HAPE

Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update

丹木斯可用於預防  re-entry HAPE(再返性HAPE)

Acetazolamide
Despite evidence that acetazolamide hastens acclimatization and blunts hypoxic pulmonary vasoconstriction in animal models and a single study in humans, no data support a role in HAPE prevention. A randomized, placebo-controlled, double-blind study of 13 healthy unacclimatized lowlanders with a history of HAPE found no significant reduction in the incidence of HAPE or pulmonary artery pressure after rapid ascent to 4559 m in those taking acetazolamide compared with placebo despite reductions in AMS and improved oxygenation.

Clinical observations suggest that acetazolamide may prevent re-entry HAPE, 
122 a disorder seen in individuals who reside at high altitude, travel to lower elevation, and then develop HAPE upon rapid return to their residence.
Recommendation
We recommend that acetazolamide not be used for HAPE prevention in those with a history of the disease during prior trips to high altitude. Strong recommendation, moderate-quality evidence.
Recommendation

We suggest that acetazolamide be considered for prevention of re-entry HAPE in people with a history of the disorder. Weak recommendation, moderate-quality evidence.


2013年 NEJM 的文章. Acute High Altitude illness 表格有寫. 類固醇可用於預防HAPE





這段是節錄自 2019 WMS update
學理上. 丹木斯應該可以預防HAPE. 但目前並無足夠研究支持這種看法
但在動物實驗和一篇人體試驗, 發現丹木斯可以降低肺動脈壓. 而肺動脈壓升高是發生高海拔肺水腫的重要機轉. 另外. 高海拔居民來到平地(低海拔)一段時間, 重新回到高海拔地區會發生"再返性高海拔肺水腫" reentry HAPE", 臨床觀察發現丹木斯能預防這種問題.

建議: 關於服用丹木斯預防HAPE. 目前缺乏研究資料, 無法證實
建議: 如果患者曾發生 reentry HAPE, 可考慮使用丹木斯預防. (如果過去不曾發生則不一定需要)

我自己的補充:
在低海拔(就是多數台灣人居住的海拔). 急性肺水腫通常來自於心臟衰竭或體液增加(例如洗腎患者), 急診室的治療. 還有小便的患者可以打利尿劑(常用的是furosemide). 將體液總量降低. 但高海拔肺水腫的患者, 往往合併全身脫水. 給予利尿劑 furosemide 不但無效. 還可能有害.
2001年NEJM的指引有一小段文章提到 furosemide. 當時認為 furosemide 無法預防 HAPE. 但對於 furosemide 是否能治療 HAPE 仍有爭議. 但 2013 年 NEJM 高海拔疾病指引, 明確寫上 furosemide 無法治療 HAPE)

Acetazolamide
Because acetazolamide hastens acclimatization, it should be effective at preventing all forms of acute altitude illness. It has also been shown to blunt hypoxic pulmonary vasoconstriction, a key factor in HAPE pathophysiology, in animal models86e88 and in a single study in humans,89 but there are no data specifically supporting a role in HAPE prevention. Clinical observations suggest acetazolamide may prevent reentry HAPE,90 a disorder seen in individuals who reside at high altitude, travel to lower elevation, and then develop HAPE upon rapid return to their residence.

Recommendation.
Because of lack of data, no recommendation can be made regarding use of acetazolamide for HAPE prevention.


Recommendation. Acetazolamide can be considered for prevention of reentry HAPE in people with a history of the disorder. Recommendation Grade: 1C


但要注意. WMS 2019 update 提到, 丹木斯不建議用於治療HAPE.

野外與登山醫學-丹木斯的兒童(指含16歲以下)劑量每次最大250mg(2024WMS指引)

2023-10-15 11:25AM
四天前(2023-10-11) WMS 發表 2024 指引更新
Wilderness Medical Society Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Acute Altitude Illness: 2024 Update
裡面提到丹木斯的兒童最大劑量是單次 250 mg(筆記在這)

2023-10-07

本來在另一篇寫兒童劑量, 但資料越放越多不方便查詢. 所以另開一篇
小兒 Pediattric 在美國FDA有定義. 指的是16歲以下, 包括嬰兒.幼兒. 幼童, 青少年都算在內.
(資料連結在這. 節錄內容 pediatric age group, from birth to 16 years, including age groups often called neonates, infants, children, and adolescents”). FDA interprets “birth to 16 years” in 21 CFR 201.57(c)(9)(iv)(A) to mean from birth to younger than 17 years old. 2023年4月26日)

在uptodate網站. acetazolamide 小兒藥物資訊, 建議的預防性最大劑量每次 125mg. 治療性的最大劑量每次 250mg
(uptodate引用的資料是 WMS 2010 指引) 

建議在最高海拔吃 2-3 天之後可停用藥物

(這是指沒有出現高海拔症狀的人)
uptodate 網站有備註. ISMM 不建議兒童例行預防使用丹木斯(但參考資料是2001年的... 也太久遠), 除非是行程無法避免海拔快速上升. 或之前曾發生過 AMS.
雖然每次吃到 500mg 仍有效益, 但因為副作用會增加. 不建議這樣使用.

下面這張圖是 2019 年WMS的指引更新
Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update

這張是預防劑量 兒童每公斤 2.5mg. 最大劑量 125mg.         

下下面這張圖下面這張圖仍是 WMS 2019 update 的內容. 
文字部分對於丹木斯的描述. 目前缺乏使用丹木斯治療兒童AMS的研究, 但傳說中(anecdotal 過去的經驗; 奇聞軼事) 是有效. 裡面提到兒童最大劑量是每次 250mg. 與表格內容不同. 

最後 2019 WMS 指引更新的結論說, 需要更多研究找出預防及治療兒童高海拔疾病的藥物處方及劑量. 因為提到兒童. 順便放上來. 
Conclusions 

We have provided evidence-based guidelines for prevention and treatment of acute altitude illnesses, including the main prophylactic and therapeutic modalities for AMS, HACE, and HAPE, and recommendations regarding their role in disease management. Although these guidelines cover many of the important issues related to prevention and treatment of altitude illness, several important questions remain to be addressed and should serve as a focus for future research. Such research includes determining the optimal rate of ascent to prevent altitude illness, the role of acetazolamide in HAPE prevention and treatment, proper dosing regimens for prevention and treatment of altitude illness in the pediatric population, and the role of staged ascent, preacclimatization, and hypoxic tents in altitude illness prevention.

ACLS-ROSC 與 sustained ROSC

2023-10-06 
ROSC 恢復自發性循環, 需脈搏跳動 30 秒以上才算
存活 Survived Event 定義, 是指 sustained ROSC 恢復脈搏持續 20 分鐘以上

參考資料來自 AHA Scientific Statement
Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports Update and Simplification of the Utstein Templates for Resuscitation Registries A Statement for Healthcare Professionals From a Task Force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Councils of Southern Africa)
Return of Spontaneous Circulation Signs of the return of spontaneous circulation (ROSC) include breathing (more than an occasional gasp), coughing, or movement. For healthcare personnel, signs of ROSC also may include evidence of a palpable pulse or a measurable blood pressure. For the purposes of the Utstein registry template, “successful resuscitation” or ROSC is defined for all rhythms as the restoration of a spontaneous perfusing rhythm that results in more than an occasional gasp, fleeting palpated pulse, or arterial waveform. Assisted circulation (eg, extracorporeal support such as extracorporeal membrane oxygenation or a biventricular assist device) should not be considered ROSC until “patient-generated” (ie, spontaneous) circulation is established. Previous reports that focused on outcomes from ventricular fibrillation have variably defined “successful defibrillation” as the termination of fibrillation to any rhythm (including asystole) and the termination of fibrillation to an organized electrical rhythm at 5 seconds after defibrillation (including pulseless electrical activity [PEA]). Neither of these definitions of successful defibrillation would qualify as ROSC unless accompanied by evidence of restored circulation. By consensus, the phrase “any ROSC” is intended to represent a brief (approximately 30 seconds) restoration of spontaneous circulation that provides evidence of more than an occasional gasp, occasional fleeting palpable pulse, or arterial waveform. The time at which ROSC is achieved is a core data element.

Survived Event 

“Survived event” for the out-of-hospital setting means sustained ROSC with spontaneous circulation until admission and transfer of care to the medical staff at the receiving hospital. For the in-hospital setting, survived event means sustained ROSC for 20 minutes (or the return of circulation if extracorporeal circulatory support is applied).