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The pathophysiology of anaphylaxis, the difference between anaphylactic and anaphylactoid reactions, and their management.

This week we continue with our discussion of anaphylaxis and will discuss its incidence in the general population and in the perioperative setting, and the mechanisms and risk factors.

1.  What is the incidence of anaphylaxis in the general population and during anesthesia?
2.  What medications have been implicated in anaphylactic reactions during anesthesia?
3.  What are the mechanisms of drug allergy?
4.  Are there any risk factors for allergic reactions?

本周我们主要讨论普通人群和围手术期过敏反应的发生率、机制和危险因素。

1.  普通人群和麻醉期间过敏反应的发生率为多少？
2.  麻醉中哪些药物与过敏反应有关？
3.  药物过敏的机制？
4.  过敏反应的危险因素有哪些？

参考答案：

1.  普通人群和麻醉期间过敏反应的发生率为多少？
法国的一项研究表明，2067名门诊的成年患者过敏发生率为14.7%，而瑞士有学者对5568名住院的成年患者研究发现，过敏发生率为17%[1]。住院患者的过敏死亡率为0.1%，而外科过敏死亡率为0.01%[1]。据报道麻醉期间药物相关的副作用发生率为1/6000～1/3500[2]，而麻醉药物导致的死亡率为6%[1]。

2.  麻醉中哪些药物与过敏反应有关？
麻醉中与过敏反应相关性最强的药物为肌肉松弛药，占60～70%[2]。其他的麻醉药物有局麻药、阿片剂，诱导药物如巴比妥类、propofol、地西泮[3]。麻醉中可导致过敏反应的药物还有包括血浆增容剂如羟乙基淀粉、抗生素、抑酞酶（多元多肽丝氨酸蛋白酶抑制剂）[3]。
近20年橡胶手套得到了广泛的使用，随着使用的增加，手套中的橡胶蛋白含量也日益增加。这是因为疾控中心对预防脱水的普遍预防，进而降低AIDS的流行。而橡胶蛋白含量和橡胶手套使用的增加成为橡胶过敏发生增多的原因之一。有调查表明由于橡胶导致的围术期过敏性休克的发生率由12.6%增加到了16.6%[2]。

3.  药物过敏的机制？
Coombs分级药物过敏反应的四种类型为[1]：
Ⅰ型为IgE介导的速发型超敏反应，即我们所说的过敏，表现为荨麻疹、血管性水肿和支气管痉挛。
Ⅱ型为IgG和IgM介导的细胞毒性反应，如细胞减少(症)和血管炎。
Ⅲ型是由IgG和IgM抗体的抗原抗体复体物介导的一种反应，如血清病和血管炎。
Ⅳ型是由淋巴细胞介导的反应如接触性皮炎。

4.  过敏反应的危险因素有哪些？
过敏反应的危险因素可分为患者因素、药物因素及其它导致过敏恶化的因素。更易在年轻人和中年女性以及有家族史或特异性体质的患者中发生[1，4，5]。给药途径也很重要，因为静脉注射过敏发生迅速且更严重。哮喘和妊娠加重药物反应[1]。

What is the incidence of anaphylaxis in the general population and during anesthesia?
A French study of 2067 adult outpatients reported an incidence of 14.7%, while a Swiss study of 5568 adult inpatients reported an incidence of 17% (1). Fatal reactions occur in 0.1% of medical inpatients and 0.01 of surgical inpatients (1). Adverse reactions to medications during anesthesia have been reported to vary from 1/6000 (1) to 1/3500 (2). The mortality of adverse reactions to drugs used for anesthesia is 6% (1).

What medications have been implicated in anaphylactic reactions during anesthesia?
The most common medications that are likely to cause an anaphylactic reaction during anesthesia are the muscle relaxants, and these account for about 60-70% of cases (2). Other medications that may cause such a reaction include local anesthetics, opioids, induction agents, such as barbiturates and propofol, and benzodiazepines (3). Agents used during an anesthetic including plasma substitutes, such as hydroxyethylstarch, antibiotics and aprotinin, a naturally occurring polybasic polypeptide serine protease inhibitor, can cause an allergic reaction (3).
Natural rubber latex gloves have been used more often during the last two decades, and the latex protein content of gloves may have increased in response to this increase in demand. This was a result of the Center for Disease Control's "Universal Precautions" for handling of body fluids, in response to the AIDS epidemic. The increased latex protein content and the increased use of latex gloves are in part responsible for the increased incidence of cases of latex anaphylaxis. One survey demonstrated that the incidence of perioperative anaphylactic shock due to latex has increased from 12.6% to 16.6% (2).

What are the mechanisms of drug allergy?
The Coombs' classification divides drug allergies into four different types (1):
•  Type I is an immediate hypersensitivity reaction that is IgE mediated. This is what we know as anaphylaxis. Presentations include urticaria, angioedema and bronchospasm.
•  Type II is a cytotoxic reaction that is IgG and IgM mediated, and examples include cytopenia and vasculitis.
•  Type III is an immune complex mediated reaction via IgG and IgM antibodies, and examples include serum sickness and vasculitis.
•  Type IV is a lymphocyte mediated reaction such as contact dermatitis.

Are there any risk factors for allergic reactions?
Risk factors for allergic reactions can be divided into patient related, drug related, and aggravating factors. They are more likely in young and middle aged females, and in patients with a positive family history or with a history of atopy (1,4,5). The route of administration is important as intravenous administration leads to a faster and more severe onset of anaphylaxis. Asthma and pregnancy may exacerbate adverse reactions to drugs (1).

References:
1.  Vervloet D, Durham S. Adverse reactions to drugs. BMJ 1998;316:1511-14.
2.  Vervloet D, Magnan A, Birnbaum J, Pradal M. Allergic emergencies seen in surgical suites. Clinical Reviews in Allergy and Immunology 1999;459-67.
3.  Vervloet D, Pradal M, Castelain M. Drug allergy. Pharmacia & Upjohn. Uppsala, Sweden 1999, 2nd edition.
4.  Kay AB. Allergy and allergic diseases. First of two parts. N Engl J Med 2001;344:30-37.
5.  Kay AB. Allergy and allergic diseases. Second of two parts. N Engl J Med 2001;344:109-13.


编辑：ache