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

2023年8月22日 星期二

201309180449anaphylaxis 全身性嚴重過敏反應 診斷標準與治療

201309180449anaphylaxis 全身性嚴重過敏反應 診斷標準與治療

另 2 篇相似內容在這裡
1. Anaphylaxis 嚴重全身性過敏反應治療藥物與頻次劑量
2. 名詞翻譯嚴重全身性過敏反應 2021-05-23

 
當確認或懷疑患者會進展為 anaphylaxis, 即使目前不完全符合 anaphylaxis 診斷標準, 仍建議施打腎上腺素, 延遲給予腎上腺素有可能導致死亡.
有一篇關於13位病危兒童的案例報告, 因食物導致的全身性嚴重過敏反應, 七名接觸過敏原之後 30 分鐘內注射腎上腺素的個案, 有一人死亡. 六位個案接觸過敏原一小時內施打腎上腺素, 有兩名死亡.
●Epinephrine should be administered as soon as possible once anaphylaxis is recognized or if impending anaphylaxis is suspected, even if patients do not meet diagnostic criteria. Delayed administration has been implicated in contributing to fatalities [1-7,67]. A study of 13 fatal or near-fatal, food-induced anaphylactic reactions in children reported that six of the seven children who survived received epinephrine within 30 minutes of ingesting the allergen, whereas only two of the six children who died received epinephrine within the first hour [2].

2021-08-30 18:31 剛好病患問epipen., 查詢了一下包裝和售價, 台灣的epipen仿單限定醫師使用(既然是醫師, 直接開一瓶 epinephrine 1mg 玻璃瓶裝就好, 一瓶可以打三次, 一支 15 台幣)
艾筆腎上腺素注射筆 0.3 毫克/次 仿單(連結在此)
台灣的進口商應該是台灣邁蘭有限公司吧? 或者它們有找其他代理商?









106年, 台灣邁蘭公司曾主動回收 epipen. 資料來源: 中華民國西藥代理商同業公會(連結在此)





Epipen劑量指南(連結在此) 這篇文章是2020-12-29更新的

一包epipen有兩套(支), 一支內裝腎上腺素0.3mg, 開封後沒有用完需丟棄(單次使用), 一包兩支價格如果以國外售價 600 美元來算, 折合台幣一萬八, 等於一支Epipen台幣9000元.

另一個網站 GoodPx (連結在此), 原廠藥在Costco賣 614.5 美金






學名藥Costco賣 309.23, 其他通路有更便宜的









2019-05-23 編輯 from uptodate.

並非要休克才能診斷成 anaphylaxis. 診斷 anaphylaxis 的意義在於盡早給予腎上腺素. 降低殘障與死亡率. 腎上腺素是 anaphylaxis 第一線用藥. 臨床醫師過度擔心腎上腺素的副作用其實往往是考慮太多. 下面三種診斷標準合乎一項要高度懷疑 anaphylaxis.

診斷標準一. 急性發作. 侵犯皮膚, 黏膜, 合併下列至少一種症狀

1. 呼吸窘迫, 例如 dyspnea, wheeze. 氣管孿縮, 喘鳴. 尖峰呼吸流速降低. 低血氧

2. 血壓降低

診斷標準二. 下列兩項以上快速發生.

1. 侵犯皮膚-黏膜組織

2. 呼吸窘迫

3. 血壓下降.

4. 持續性腸胃道症狀. 腸絞痛. 嘔吐.

診斷標準三, 暴露於過敏原數分鐘至數小時內血壓下降

1. 成人血壓 < 90. 或比基礎值降低 30%

2. 嬰兒與兒童, 收縮壓降低. 或比基礎值降低 30%

Anaphylaxis: Emergency treatment 過敏性休克的急診治療
Authors:Ronna L Campbell, MD, PhDJohn M Kelso, MDSection Editors:Ron M Walls, MD, FRCPC, FAAEMAdrienne G Randolph, MD, MScDeputy Editor:Anna M Feldweg, MD
All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Apr 2019. | This topic last updated: Nov 14, 2018.

INTRODUCTION anaphylaxis(應翻譯成嚴重全身性過敏反應,而非一定要休克)是潛在致死性的疾病, 常常被低估, 治療不足, 原因可能是因為 anaphylaxis 是一個廣泛症候群, 比過敏性休克更廣義. 治療目標是早期辨識, 使用腎上腺素避免惡化至危及生命的呼吸或心血管症狀及徵象, 包括休克.
Anaphylaxis is a potentially fatal disorder that is under-recognized and undertreated. This may partly be due to failure to appreciate that anaphylaxis is a much broader syndrome than "anaphylactic shock," and the goal of therapy should be early recognition and treatment with epinephrine to prevent progression to life-threatening respiratory and/or cardiovascular symptoms and signs, including shock.

This topic will discuss the treatment of anaphylaxis. The clinical manifestations and diagnosis of anaphylaxis, pathophysiology, and unique features of anaphylaxis in specific patient groups are reviewed separately:

醫院外使用腎上腺素的劑量分開討論

Recommendations for dosing and prescribing epinephrine for use by patients and caregivers in the community setting are provided separately.

IMMEDIATE MANAGEMENT 立即治療

適當的評估及治療對於anaphylaxis很重要, 呼吸或心臟停止可能在數分鐘內發生, 適當的治療 anaphylaxis 很重要, 早期治療最有效, 太晚給予腎上腺素, 病患可能會死亡.
Prompt assessment and treatment are critical in anaphylaxis, as respiratory or cardiac arrest and death can occur within minutes [1-9]. It is also important to treat anaphylaxis promptly because it appears to be most responsive to treatment in its early phases, based on the observation that delayed epinephrine injection is associated with fatalities.

The tables provide rapid overviews of the initial assessment and emergency management of anaphylaxis in adults (table 1) and in children (table 2).

table 2 列出的危險徵象, 主要是臨床診斷(不需要抽血或影像檢查), 最常見的是皮膚症狀(例如突發性全身蕁麻疹, 血管性浮腫, 潮紅, 搔癢). 但有 10-20% 病患沒有皮膚症狀, 所以不能以此排除.

danger signs: 危險徵象包括: 症狀快速進展, 出現呼吸窘迫(喘鳴, 嘯鳴, 呼吸困難, 呼吸費力, 胸部周圍皮膚往內凹陷, 持續咳嗽, 循環不良的現象, 腹痛, 嘔吐, 心律不整, 低血壓, 昏倒.
胸部周圍皮膚內陷, 是因為呼吸道黏膜腫脹, 所以胸腔擴張時, 外界空氣無法進入, 使得胸部負壓過大
持續咳嗽可能是小支氣管黏膜腫脹引起
腹痛, 嘔吐可能是過敏性血管炎引起

緊急處置

首先最重要的治療是給予腎上腺素, 在緊急情況, 腎上腺素沒有絕對禁忌症(沒有什麼情況絕對不能給腎上腺素). 正常人, 如果給予腎上腺素, 可能會引起腦出血, 腦室內出血, 急性心肌梗塞等等併發症, 但遇到anaphylaxis 的病患, 如果沒給腎上腺素, 病患可能立即死亡, 所以以上都不是考量的重點.

呼吸道: 如果因血管性浮腫,病患即將發生呼吸道阻塞, 應立即早期插管, 因為稍晚一點, 可能變成完全呼吸道阻塞, 成為困難插管個案, 插管建議由最有經驗的醫師執行, 並隨時準備建立外科呼吸道.

肌肉注射腎上腺素: 從大腿外側, 給予每公斤 0.01mg 腎上腺素, 對於體型較大的兒童, 最大劑量 0.5mg. 根據給藥之後的反應, 每 5-15 分鐘可以再注射一次 (2005 ACLS 指引建議 15-20 分鐘打 0.3~0.5mg)(也可以給更頻繁), 如果施打適當, 病患在打完第一支, 第二支, 最多第三支之後應該會改善, 如果持續呈現循環不良的徵象, 或病患症狀在肌肉注射之後沒有改善, 準備靜脈注射腎上腺素.

病患擺位: 平躺, 如果可以的話將雙腳抬高更好. 類似 lithotomy position.
氧氣: 從氧氣面罩每分鐘 8-10 L開始, 根據SpO2調整, 直到 NRM 10-15L/min (FiO2 100%).


生理食鹽水快速滴注: 循環不良的患者, 每公斤給予 20cc 生理食鹽水, 成人 60 公斤給 1200cc. 70 公斤給 1400 cc. 給完之後迅速評估, 仍循環不良者, 可再次給予每公斤 20 cc, anaphylaxis 患者, 血管內的水分可能大量移動到血管外, 給水的過程需監測尿液出來的量.

albuterol 對於腎上腺素反應不良的氣管孿縮, 可給予氣管擴張劑, albuterol 0.15 mg/kg (最低劑量 2.5 mg) 加 3 mL saline, 可重複給予. 20公斤重的兒童給予 3mg. 50公斤成人給予 7.5mg, 60公斤重成人給予 9mg.

H1B 抗組織胺第一型拮抗劑: 醫院最常使用的是 diphenhydramine(常見商品名是 vena). 每公斤給 1mg. 最大給 40 mg (不過一支 vena 通常是 30 mg...乾脆給 60 mg 比較好算).

H2B 抗組織胺第二型拮抗劑: 臨床上通常是拿來治療胃炎或潰瘍, 可以給 ranitidine 每公斤 1mg, 最大 50 mg. 靜脈注射(anaphylaxis病患,黏膜如果水腫, 口服吸收效果可能受影響, 且嘔吐病患無法口服).

皮質類固醇: methylprednisolone 1 mg/kg (max 125 mg) IV, 我們醫院有兩種靜脈注射的劑量, 一種是 40mg, 一種是 500mg. 以前舊的資料說可以給 125-500 mg. 緊急狀況我想我會直接給一瓶 500 mg. 不用慢慢算要打幾分之幾瓶

頑固性症狀的治療: 原則上所有升壓劑都要用機器幫浦給藥.
(但有原則就有除外, 關於 dirty epi drip 請看這篇 https://www.aliem.com/dirtyepi/)
(EMNote上面有介紹 push dose epinephrine 即是 dirty epi drip https://www.emnote.org/emnotes/push-dose-epinephrine)

腎上腺素靜脈滴注, epinephrine 注射劑量 0.1 to 1 ug/kg/minute, 如果用一支 1mg= 1000 ug, 泡 100 cc 生理食鹽水, 60公斤成人, 每分鐘每公斤 0.1ug 開始算. 60 * 60 * 0.1, 一小時給 360 ug. 使用pump(台灣的點滴幫浦通常是用每小時幾cc計算). 每小時 run 36cc. 腎上腺素最好從大條靜脈給. 以免漏針之後造成局部組織缺血壞死.

除了給予腎上腺素, 還可以加入第二種升壓劑, 通常選 levophed(norepinephrine).

Vasopressors: Patients may require large amounts of IV crystalloid to maintain blood pressure. Some patients may require a second vasopressor (in addition to epinephrine). All vasopressors should be given by infusion pump, with the doses titrated continuously according to blood pressure and cardiac rate/function monitored continuously and oxygenation monitored by pulse oximetry.




初步治療的基石如下:

移除造成過敏的原因

求救 (召集院內急救團隊, 或打 119)

肌肉注射腎上腺素

讓病患平躺, 下肢抬高, 除非病患有上呼吸道腫脹問題, 需坐直保持呼吸道通暢, 嘔吐的病患, 讓病患側躺躺同時將下肢抬高, 病患如果懷孕中晚期, 肚子比較大, 可以讓他們左側朝下側躺.

給氧氣

給予靜脈輸液 1000 cc

The cornerstones of initial management are the following [16-21]:

●Removal of the inciting cause, if possible (eg, stop infusion of a suspect medication).

●Call for help (summon a resuscitation team in a hospital setting or call 911 or an equivalent emergency medical services number in a community setting).

●Intramuscular (IM) injection of epinephrine at the earliest opportunity, followed by additional epinephrine by IM or intravenous (IV) injection.

●Placement of the patient in the supine position with the lower extremities elevated, unless there is prominent upper airway swelling prompting the patient to remain upright (and often leaning forward). If the patient is vomiting, placement of the patient semirecumbent with lower extremities elevated may be preferable. Place pregnant patients on their left side.

●Supplemental oxygen.

●Volume resuscitation with IV fluids.

在一項 164 位死亡病例的研究, 從症狀發作到呼吸/心跳停止的中位數時間, 醫源性嚴重過敏是 5 分鐘, 昆蟲螫咬造成嚴重過敏是 15 分鐘, 食物造成的嚴重過敏時間是 30 分鐘.

In a series of 164 fatalities due to anaphylaxis, the median time interval between onset of symptoms and respiratory or cardiac arrest was 5 minutes in iatrogenic anaphylaxis, 15 minutes in stinging insect venom-induced anaphylaxis, and 30 minutes in food-induced anaphylaxis [1]. A more detailed review of fatal anaphylaxis is presented elsewhere.

初步評估與處置

Initial assessment and management — A number of critical components in the initial management needs to be instituted concomitantly [22-27]. Rapid overview tables that summarize important interventions in the first few minutes of management are provided for adults (table 1) and for infants and children (table 2):

首先要注意病患是否出現呼吸道問題, 呼吸是否正常, 循環是否正常, 神智是否正常, 評估嘴唇, 舌頭, 口咽是否出現血管性浮腫, 請病患說出自己姓名, 以評估聲門上及聲門是否有腫脹, 檢查病患皮膚是否有蕁麻疹或血管性浮腫, 這些都有助於診斷.

●Initially, attention should focus on airway, breathing, and circulation, as well as adequacy of mentation. The lips, tongue, and oral pharynx are assessed for angioedema, and the patient is asked to speak his or her name to assess periglottic or glottic swelling. The skin is examined for urticaria or angioedema, which (if present) is helpful in confirming the diagnosis.

下面是Uptodate 的 TABLE 1 .




在大腿外側肌肉注射腎上腺素, 如果症狀嚴重, 可考慮靜脈注射腎上腺素

●Epinephrine should be injected IM into the mid-outer aspect of the thigh (table 1 and table 2) . If symptoms are severe, an IV epinephrine infusion should be prepared.

如果上呼吸道沒有水腫, 讓病患平躺, 下肢抬高, 以提高重要器官的血液循環, 中期或晚期的懷孕婦女可以左側朝下側躺, 減少子宮對下腔大靜脈的壓迫, 平躺的姿勢有助於改善嚴重低血壓, 改善心臟血液填充, 改善無脈搏心臟收縮, 這種嚴重的狀況, 病患可能在數秒內死亡. 呼吸窘迫或嘔吐病患可能無法忍受平躺, 以病患覺得舒服的姿勢休息即可. 下肢盡可能抬高.

●If the upper airway is not edematous, the patient should be placed in the recumbent position, with the lower extremities elevated to maximize perfusion of vital organs (and pregnant patients on their left side to minimize compression of the inferior vena cava by the gravid uterus) [30]. The recumbent position also helps prevent severe hypotension, subsequent inadequate cardiac filling, and pulseless cardiac activity. In this situation, death can occur within seconds [21]. Individuals with respiratory distress or vomiting may not tolerate the recumbent position and should be placed in a position of comfort, with lower extremities elevated, if possible.

氧氣使用, 一開始可以選 NRM 15L/每分鐘, 或高流量氧氣面罩, 提供 FiO2 > 70% ~ 100%

●Supplemental oxygen, initially using a nonrebreather mask at 15 liters/minute flow rate or commercial high flow oxygen masks (providing at least 70 percent and up to 100 percent oxygen) should be administered.

建立兩條大條的靜脈管路(在成人最好是 14-16號)

●Two large-bore IV catheters (ideally 14 to 16 gauge for most adults) should be inserted in preparation for rapid administration of fluids and medications. Intraosseous access should be obtained if IV access is not readily obtainable.

血壓正常的成人, 可給予每小時 125 cc 生理食鹽水靜脈注射, 血壓正常的小孩, 可依照體重給予能保持靜脈通暢的輸液

●In normotensive adults, isotonic (0.9 percent) saline should be infused at a rate of 125 mL/hour to maintain venous access. In normotensive children, isotonic saline should be infused at an appropriate maintenance rate for weight in order to maintain venous access.

持續性監測心電圖, 血壓, 心跳, 呼吸速率, 血氧濃度

●Continuous electronic monitoring of cardiopulmonary status, including frequent measurements of blood pressure (BP), heart rate, and respiratory rate, as well as monitoring of oxygen saturation by pulse oximetry, is required for the duration of the episode.



下面是 emedicine 的資料



腎上腺素的爭議比較少, 僅列出抗組織胺和類固醇的敘述.



Administration of Antihistamines and Corticosteroids 標準的 anaphylaxis 治療包含抗組織胺與類固醇, 但抗組織胺的作用時間比腎上腺素慢, 對血壓影響也小, 不可以僅用抗組織胺來治療 anaphylaxis,. 抗組織胺可做為腎上腺素的輔助治療.
The standard treatment of anaphylaxis should also include antihistamines and corticosteroids. However, antihistamines have a much slower onset of action than epinephrine, they exert minimal effect on blood pressure, and they should not be administered alone as treatment. [73] Antihistamine therapy thus is considered adjunctive to epinephrine.



給予H1B 及 H2B, 兩種合併使用效果, 對於緩解組織胺引起的症狀優於單獨使用H1B, 通常選擇 diphenhydration + ranitidine, 如果血液循環不佳, 腸胃或肌肉吸收可能不佳, 靜脈注射較能確保有效的藥物劑量進入血中, 但對於輕微的 anaphylaxis, 口服或肌肉注射就足夠了.



Administer an H1 blocker and an H2 blocker, because studies have shown the combination to be superior to an H1 blocker alone in relieving the histamine-mediated symptoms. Diphenhydramine and ranitidine are an appropriate combination. IV administration ensures that effective dosing is not impaired by hemodynamic compromise, which adversely affects gastrointestinal (GI) or IM absorption. However, oral or IM administration of antihistamines may suffice for milder anaphylaxis.



類固醇對於anaphylaxis 沒有立即效果, 但早期給予類固醇可避免潛在的晚期反應(雙相的anaphylaxis), 已經因其他疾病正在使用類固醇的人, 發生 anaphylaxis 之後更可能進展成致命性的 anaphalaxis, 給予更多的類固醇對於此類病患會有好處, 作者建議所有anaphylaxis病患都應該給予類固醇, 如果擔心吸收不良, 可考慮靜脈注射.



Corticosteroids have no immediate effect on anaphylaxis. [74] However, administer them early to try to prevent a potential late-phase reaction (biphasic anaphylaxis). Patients with asthma or other conditions recently treated with a corticosteroid may be at increased risk for severe or fatal anaphylaxis and may receive additional benefit if corticosteroids are administered to them during anaphylaxis. The authors recommend corticosteroid treatment for all patients with anaphylaxis. If absorption is a concern, IV preparations should be used.



多數病患使用抗組織胺及類固醇, 可完全改善, 類固醇在接下來數天內可慢慢減低劑量, 但有些病患可能需長期使用預防性的高劑量 H1B



Most patients treated with antihistamines and steroids have complete remission following tapering of steroids. Others require long-term prophylaxis with high doses of H1 antihistamines.



在一次急性發作之後, 出院或門診治療的藥物, 可給予口服抗組織胺, 給予數天類固醇, 但這些藥物僅是理論上有用, 並無大規模研究證實其療效.



Outpatient medications are the oral forms of antihistamines and corticosteroids that should be continued for a short time (a few days) following an episode. The benefit of these drugs is more theoretical because no studies exist that prove their benefit in this setting.



prednisolone 是相當方便的口服類固醇, 但沒有研究證實最佳劑量是多少, 成人可以給每天每公斤 1mg, 分幾次吃, 小孩可以給每天每公斤 0.5-1 mg,. 分幾次吃. 如果只吃數天, 不需要慢慢減量, 長期服用才需要逐漸減量.



A convenient oral corticosteroid is prednisone. No proven best dose exists. In adults, a dose of 1 mg/kg/d in divided doses is probably adequate; in children, a dose of 0.5-1 mg/kg/d in divided doses is appropriate. Tapering is not necessary unless the patient has been taking steroids chronically.



底下的處方是臨床醫師常用的, 但沒有很強的證據支持這樣用對於急診病患有效, 所以不要將下列處方視為唯一標準處方, 尤其是關於 H2B 的療效的研究更少.



The following regimens are used commonly by clinicians, though very little hard data concerning the natural history of anaphylaxis treated in the ED exists. In light of this, do not construe the following as an unqualified recommendation or as a standard of care. Evidence for efficacy of H2 -blocker antihistamines is particularly sparse.



H1 -blocker antihistamine treatment is as follows:



Diphenhydramine (Benadryl)- Adults: 25 mg PO q6h for 2-5 d; Children: 1 mg/kg PO q6h for 2-5 d



Hydroxyzine (Atarax)- Adults: 25 mg PO q8h for 2-5 d; Children: 1 mg/kg PO q8h for 2-5 d



Corticosteroid treatment is as follows:



(這裡舉 prednisone 也很奇怪, prednisone 需要在體內代謝成 prednisolone, 才有生理活性, 不過這兩者的等效劑量是相同的)



Prednisone - Adults: 20-80 mg PO daily for 2-5 d; Children: 0.5-1 mg/kg PO daily for 2-5 d



Many other glucocorticoid preparations may be used.



H2 -blocker antihistamine treatment is as follows:



Cimetidine 這個劑量比較奇怪, 台灣通常是一顆 400 mg 或注射型 2CC= 200 mg.



Cimetidine - 300 mg PO qid for 2-5 d; Children: Not recommended



常發生不明原因 anaphylaxis 的人, 可考慮每天服用抗組織胺 (H1B + H2B). 更少部分的人, 可能須服用類固醇來降低發作頻率.



Patients with frequent idiopathic anaphylaxis may benefit from daily antihistamine therapy (both H1 antagonists and H2 antagonists) or, in rare circumstances, daily corticosteroid therapy.



每天服用的抗組織胺, diphenhydramine 或 hydroxyzine 是常見選擇, 二代抗組織胺較不具嗜睡作用, 二代抗組織胺劑量: fexofenadine(艾來 allegra) 每天 180mg, loratadine(claritin) 每天 10mg, cetirizine (zyrtec) 每天 10 mg. des-loratadine (clarinex) 每天 5mg. levocetirizine(xyzal) 每天 5mg. 然而這些藥物是否能預防 anaphylaxis 並沒有被證實, 有些免疫專家會開更大劑量的抗組織胺給病患(在病患可忍受副作用的範圍內)



For daily antihistamine therapy, diphenhydramine or hydroxyzine is often used first. Second-generation, less-sedating agents may be preferable because of decreased adverse effects. In their adult doses, these include fexofenadine (Allegra) at 180 mg/d, loratadine (Claritin) at 10 mg/d, cetirizine (Zyrtec) at 10 mg/d, desloratadine (Clarinex) at 5 mg/d, and levocetirizine (Xyzal) at 5 mg/d. However, none has been specifically evaluated in anaphylaxis prevention. Some specialists prescribe extra doses of antihistamines as needed and as tolerated to control symptoms.



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底下是uptodate 舊的資料

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Anaphylaxis is highly likely when any one of the following three criteria is fulfilled:

Criterion 1 — Acute onset of an illness (minutes to several hours) involving the skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula) and at least one of the following:

●Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory flow, hypoxemia)

OR

●Reduced blood pressure (BP) or associated symptoms and signs of end-organ malperfusion (eg, hypotonia [collapse], syncope, incontinence)

Note that skin symptoms and signs are present in up to 90 percent of anaphylactic episodes. This criterion will therefore frequently be helpful in making the diagnosis.

Criterion 2 — Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):

●Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula).

●Respiratory compromise (eg, dyspnea, wheeze/bronchospasm, stridor, reduced peak expiratory flow, hypoxemia).

●Reduced BP or associated symptoms and signs of end-organ malperfusion (eg, hypotonia [collapse], syncope, incontinence).

●Persistent gastrointestinal symptoms and signs (eg, crampy abdominal pain, vomiting).

Note that skin symptoms or signs are absent or unrecognized in up to 20 percent of anaphylactic episodes. Criterion 2 incorporates gastrointestinal symptoms in addition to skin symptoms, respiratory symptoms, and reduced BP. It is applied to patients with exposure to a substance that is a likely allergen for them.

Criterion 3 — Reduced BP after exposure to a known allergen for that patient (minutes to several hours):

●Reduced BP in adults is defined as a systolic BP of less than 90 mmHg or greater than 30 percent decrease from that person's baseline

●In infants and children, reduced BP is defined as low systolic BP (age-specific)* or greater than 30 percent decrease in systolic BP

* Low systolic BP for children is defined as:

•Less than 70 mmHg from 1 month up to 1 year

•Less than (70 mmHg + [2 x age]) from 1 to 10 years

•Less than 90 mmHg from 11 to 17 years

Note that criterion 3 is intended to detect anaphylactic episodes in which only one organ system is involved and is applied to patients who have been exposed to a substance to which they are known to be allergic (for example, hypotension or shock after an insect sting).

There will be patients who do not fulfill any of these criteria but for whom the administration of epinephrine is appropriate. As an example, it would be appropriate to administer epinephrine to a patient with a history of near-fatal anaphylaxis to peanut who presents with urticaria and flushing that developed within minutes of a known or suspected ingestion of peanut [10].

下面是ACLS 章節關於嚴重過敏性反應的討論

Discussion

Consensus Statements
1. "The Traditional Mechanistic Definition of Anaphylaxis is not Useful at the Bedside." When asked to define anaphylaxis, even some allergists have admitted that, "Anaphylaxis is hard to define, but I know it when I see it." However, other clinicians might not recognize anaphylaxis on instinct alone.

Discussion: There is a "disconnect" in how anaphylaxis has historically been defined and how the term is used clinically. Traditionally, allergy textbooks and guidelines have defined anaphylaxis mechanistically—based on immunoglobulin E levels, mast cells, basophils, cytokines, and inflammatory mediators. However, that approach is not helpful at the bedside; and the issue is further compounded by existing clinical definitions that are, themselves, variable. Anaphylaxis has been defined clinically as reactions that range from mild—such as simple urticaria—to life-threatening—such as those involving hypotensive shock.

The definition of anaphylaxis affects all aspects of clinical practice—from when to consider it as a diagnosis to how to manage the patient, from how to code a serious allergic reaction to how to design an appropriate clinical trial. It is our consensus that the traditional mechanistic definition of anaphylaxis is not useful for non-allergists, and acknowledging this is the starting point to improving care of the anaphylaxis patient in the prehospital and ED settings.

Whether or not an enhanced definition will improve care is not known. Will better recognition and standard protocols yield fewer deaths from anaphylaxis or decreased risks of hospitalization or recurrence? Data are needed. What is known, however, is that almost all studies of anaphylaxis care in the ED identify the lack of, or inconsistency in, definition and criteria as a significant contributing factor to poor patient outcomes.

2. Most Acute Episodes of Anaphylaxis are Managed by ED Clinicians and not by Allergists. The diagnosis and management of anaphylaxis in the ED differs from that in the allergy clinic.

Discussion: Although the majority of the anaphylaxis literature—including guidelines and practice parameters—is published in allergy journals, the ED is the most common clinical setting for treating anaphylaxis. A review of anaphylaxis in children and adolescents over a 6-year period reported that 71% of cases were treated in the ED or in an urgent care center.[7] The number of annual ED visits for anaphylaxis in the US is estimated to be as high as 500,000.[4] However, multiple reviews and surveys of care provided in emergency settings have reported low concordance with guideline-recommended treatment, even in patients who were clearly diagnosed with anaphylaxis by medical record or by International Classification of Diseases, 9th Edition (ICD-9) code.

3. Anaphylaxis is Under-diagnosed (And, Hence, Under-treated) in Most Prehospital Care Situations and EDs.[4,19] Discussion: The reported incidence of anaphylaxis in the EM literature is likely to be an underestimate of the true incidence, due to inconsistent use of consensus definitions and inaccurate ICD-9 coding.[4,19] Anaphylaxis has a wide range of clinical presentations, and different diagnostic criteria (even different coding practices) may be applied among health care systems. By way of example, the number of diagnosed anaphylaxis cases was estimated to increase by 58% when a validated ICD-9-Clinical-Modification-based diagnostic algorithm that included anaphylactic signs and symptoms was applied to ED data from the Florida Agency for Health Care Administration (2005–2006).[14] Similarly, an earlier study evaluating the application of anaphylaxis coding to acute allergic reactions between 1993 and 2004 reported that 51% of 678 ICD-9-coded food-induced acute allergic reactions were actually anaphylaxis.

One identified problem is a limited ability of ICD codes to differentiate between various types and severities of allergic reactions in the ED. A 2012 review of pediatric records in a New York City ED reported that 213 patients met the Second Symposium criteria for anaphylaxis (see Table 1 ), but only 62 (29.1%) were actually coded as anaphylaxis.[20] The majority (75%) were coded as "allergic reaction." This type of under-diagnosis of anaphylaxis in the ED is not new. An earlier review of more than 19,000 ED visits identified 17 cases that met the criteria for anaphylaxis; but only four (23.5%) were diagnosed as such in the ED.[18] That report, published in 1995, suggested the need for a standard definition and encouraged better clarity in the diagnostic criteria used to differentiate anaphylaxis from a diagnosis of "allergic reaction," recommendations that were repeated in the 2012 survey.

4. It is Important for Prehospital and EM Providers to Recognize That a Patient can Have Anaphylaxis Without Shock. Discussion: Data suggest that the diagnosis of "allergic reaction" is often used by Emergency Physicians for patients who should have received a diagnosis of anaphylaxis.[14–16,18–21] As noted previously, this may reflect a general lack of awareness of the spectrum of severity in anaphylaxis, the inaccuracies of current coding systems, or the absence of prospectively validated diagnostic criteria for anaphylaxis.[4,6] There may also be a tendency by some health professionals to equate anaphylaxis with shock.

It is important to recognize that the patient may not present with life-threatening symptoms. The initial clinical presentation may be simply gastrointestinal complaints plus hives, or gastrointestinal distress with difficulty breathing. However, anaphylaxis occurs as a continuum, so that even when the initial symptoms are mild, there is significant potential for rapid progression to a severe reaction, which may prove fatal. It often is impossible to predict the ultimate severity of an anaphylactic episode at the time of onset.[22] Any delay in appropriate treatment increases the potential for morbidity and mortality.

5. Anaphylaxis Causes Significant Morbidity and can be Fatal. Discussion: It has been estimated that approximately 1500 persons die annually in the US related to anaphylactic reactions to foods, drugs, latex, and insect stings.[25] This translates to an annual mortality incidence rate between 0.002% and 1%.[13,25] Although this is a low mortality rate, appropriate anaphylaxis management should be of great concern because many of these reactions have the potential to be fatal, and the patients who succumb are often young and otherwise in good health. Death usually occurs due to circulatory collapse or respiratory arrest, and may occur so rapidly that patients do not present with classic symptoms.

Contributing to the challenge, there is no single test to diagnose anaphylaxis or predict its outcome. For this reason, it is critical that all emergency professionals not only appreciate the potential morbidity and life-threatening nature of anaphylaxis, but also recognize the multiple factors (and cofactors) that can increase the likelihood of an acute episode as well as its severity and risk of fatality ( Table 2 ).

Prompt recognition and aggressive treatment—particularly the early administration of intramuscular (i.m.) epinephrine—will, in most cases, reduce the severity and associated morbidity of the acute episode.[1–3,12,23,24,28] Withholding epinephrine in favor of antihistamine, steroid administration, and "watchful waiting," or even establishing intravenous access in patients with a reasonable suspicion of anaphylaxis is risky—even in the presence of mild presenting symptoms.

6. Epinephrine Should be the First-line Treatment for all Prehospital and ED Patients With Anaphylaxis. Early administration is critical. All current guidelines recommend that when a patient experiences a reaction that a health care provider considers as possible anaphylaxis, it is generally better to err on the side of caution and administer epinephrine.

Discussion: The first-line use of epinephrine is the standard of care for anaphylaxis and is a clear directive in all guidance documents published in the past two decades.[1–3,12,23,24,28] However, concordance varies widely. In surveys of EM practice, the proportion of patients with severe allergic reactions or anaphylaxis who received epinephrine ranged from as low as 12% to almost 80%. This probably reflects the fact that epinephrine is often not given to patients who do not have life-threatening cardiovascular (e.g., "shock") or respiratory symptoms, as these patients, by many health system definitions and coding, are not considered to have anaphylaxis.[8,9] The question of who should be treated with epinephrine has been further complicated by controversy in older guidelines that questioned the use of epinephrine for milder reactions (e.g., single organ involvement, cutaneous symptoms only).

The current body of evidence supports the use of i.m. epinephrine as first-line treatment for anaphylaxis for all patients rather than alternative routes such as subcutaneous or intravenous (i.v.). Delaying administration of epinephrine has been associated with increased reaction severity, increased morbidity, a greater likelihood of biphasic reactions, and an increased risk of fatality even in some cases in which the initial symptoms were mild.

The use of additional medications depends on the severity of the reaction and the initial response to epinephrine. Oral antihistamines are second-line supportive therapy with a slow (1 h or longer) onset of action. They may be useful to control cutaneous manifestations of an anaphylactic reaction.An inhaled beta-agonist can be used as adjunctive therapy for patients with pre-existing asthma who present with respiratory symptoms.Corticosteroids have not been shown to be effective for the acute treatment of anaphylaxis, but are sometimes used to reduce the likelihood of protracted anaphylaxis or recurrent reactions. There are no data to support these uses of corticosteroids, and further studies are warranted.

7. There are no Absolute Contraindications to the use of Epinephrine for Anaphylaxis. Serious Adverse Effects are Very Rare When Epinephrine is Administered at the Appropriate Intramuscular Doses for Anaphylaxis. Discussion: Epinephrine is a direct-acting sympathomimetic agent that targets multiple organs by interacting with alpha- and beta-adrenergic receptors. Its clinical effects include vasoconstriction, decreased mucosal edema, increased inotropy, chronotropy, and bronchodilation. Epinephrine also down-regulates the continued release of mediators of anaphylaxis from mast cells and circulating basophils. The common transient side effects include pallor, tremor, anxiety, headache, and palpitations.

Intramuscular injection into the anterolateral thigh, the preferred route of administration for epinephrine to treat anaphylaxis, attains higher plasma levels more quickly than subcutaneous administration.[1,2,12,33] The dose is 0.01 mg/kg of a 1:1000 (1 mg/mL) solution to a maximum of 0.5 mg in adults or 0.3 mg in children. Depending on the severity of the episode and the response to the initial injection, this dose can be repeated every 5–15 min as needed; most patients respond to one or two doses.

Fear of serious adverse effects is a commonly cited concern with epinephrine and probably contributes to its under-usage for anaphylaxis. However, the reality is that epinephrine toxicity is much more likely to occur with i.v. administration, particularly at high doses or rapid infusion rates. The severe physiologic responses seen in i.v. epinephrine (e.g., ventricular dysrhythmias, hypertensive crisis, pulmonary edema) are rare when using the preferred i.m. route and recommended dose for anaphylaxis. Using an epinephrine auto-injector, which delivers a pre-filled therapeutic dose, may allay some of the concerns related to confusion between epinephrine i.v. dosing for cardiopulmonary resuscitation (1:10,000 dilution) and i.m. dosing by syringe (1:1000 dilution). However, although extremely rare, acute ST-elevation myocardial infarction can occur, even with therapeutic i.m. epinephrine, and in the ED setting, hemodynamic monitoring is important .

In-depth discussion of the pharmacology and adverse effects of epinephrine is beyond the scope of this article. The reader is referred to the current guidelines and practice parameters, as well as several excellent reviews for more information.

8. Anaphylaxis is a Long-term Diagnosis, and Management Does not End With Discharge From the ED. Patients are at risk for more episodes, and most episodes occur in the community, not in the medical setting.

Discussion: Anaphylaxis is a condition that carries the persistent risk of acute and potentially life-threatening episodes. Treating the acute event in the ED can be a first step towards reducing the risk, though prospective data are needed. All current guidelines recommend that patients treated in the ED for anaphylaxis should be discharged with an epinephrine auto-injector (or a prescription for an auto-injector), personalized written instructions about anaphylaxis to help them recognize symptoms, avoid triggers, and understand how to inject epinephrine, and a referral (preferably, allergist) for follow-up and long-term care.

9. Outcomes Data are Needed. A limited body of evidence exists demonstrating possible practice gaps in the management of anaphylaxis in the ED setting.

Discussion: Based on the current body of evidence, it can be inferred that how anaphylaxis is managed in the emergency setting frequently does not concur with guideline recommendations. The data are largely indirect—from case reports and retrospective reviews of medical databases—and do not answer key questions about patient outcomes, such as:

What data show that not using epinephrine quickly results in more hospitalizations? Or increased morbidity, or recurrence?

How do the outcomes for patients given antihistamines first for an anaphylaxis episode compare to patients treated immediately with epinephrine?

Do patients who do not (re)fill epinephrine prescriptions do worse than patients who maintain their epinephrine and keep it with them?

Prospective studies are needed

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