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 focus on its differential diagnosis. In addition, we will explore the association between asthma and allergy.
You are in the preadmission test center, seeing a 47 years-old white female scheduled for a laparoscopic cholecystectomy. Her past medical history is remarkable for asthma and she tells you that during her last anesthetic, a cone biopsy 5 years ago, the anesthesiologist experienced a difficult time "trying to move oxygen into and out of my lungs". She also states that she is allergic to morphine and codeine.
1. Is there any association between asthma and drug allergy?
2. What do you make out of the difficulty trying to ventilate her during a prior anesthetic?
3. How do you differentiate between bronchoconstriction from asthma and anaphylaxis?
本周我们继续讨论过敏反应，重点是鉴别诊断，此外，将讨论哮喘和变态反应的关系。
院前检查中心接诊一47岁白人女性，计划实施腹腔镜胆囊切除术。其有明确的哮喘病史，且主诉在5年前行锥形活组织检查接受麻醉时，肺通气出现“氧气进出肺部困难”。同时患者明确表示对吗啡和可待因过敏。
1. 哮喘和药物过敏间是否有联系？
2. 在该患者上次麻醉中出现通气困难时你怎样做？
3. 如何鉴别哮喘的支气管收缩和过敏反应？
参考答案：
1. 哮喘和药物过敏间是否有联系？
过去几年过敏性哮喘发生率增加，最近的新英格兰杂志发表了关于过敏和变应性疾病的综述，哮喘和过敏反应是两种完全不同的变应性疾病[1，2]。绝大多数哮喘患者属于特应性，特应性指IgE介导的疾患。具有特异质的患者更易出现药物过敏，发生过敏反应。也有关于使用单克隆抗IgE抗体治疗过敏性哮喘，这更进一步的证明了过敏性哮喘至少部分是因为IgE抗体所介导[3]。
2. 在该患者上次麻醉中出现通气困难时你怎样做？
患者的主诉提示在其上次接受麻醉过程中发生了支气管痉挛，但患者提供的信息可能有部分并不准确，因此，必须查阅既往的麻醉记录。假设其真的发生了支气管痉挛，很难区分究竟是过敏还是急性哮喘发作。哮喘是气道对非特异性刺激具有高反应性为特点的一种疾患，如气管插管等刺激可导致支气管收缩。如前讨论所述，过敏反应也可出现支气管收缩。在抗原作用下，组织肥大细胞和循环嗜碱粒细胞释放介质表示发生临床过敏反应。这些介质包括组胺（可导致支气管平滑肌收缩增加）、中性蛋白酶如纤维蛋白溶酶。
非特异性非免疫性组胺释放可导致支气管痉挛。该患者IgE基础值可能较高，肌松剂和吗啡等药物可导致组胺释放，致支气管平滑肌收缩。阿片剂过敏非常少见。该患者可能对阿片剂出现非特异性组胺释放，明确患者所描述的“过敏”的真正意思将有助于病情判断，如部分患者叙述的副作用，如恶心、呕吐。
虽然其他可能导致支气管收缩的可能性较小，但也应考虑，包括右主支气管阻塞、麻醉深度不足、气胸、肺水肿和肺栓塞[4]。
3. 如何鉴别哮喘的支气管收缩和过敏反应？
很难将支气管收缩同哮喘、过敏反应真正区分开来，因为支气管痉挛可能是过敏反应的唯一表现，可在麻醉诱导给药或接触橡胶时发生。其他表现如血管性水肿、全身荨麻疹和心血管性虚脱提示出现过敏反应。支气管痉挛的发生和气管插管有一定的相关性。虽然气管插管后即刻表现更可能是急性哮喘发作，但也不能排除过敏反应[4]。与气管插管无关的支气管痉挛更可能是发生过敏，特别是当使用某种新药后。
一种纤维蛋白溶酶和抗原特异性IgE抗体可有助于诊断。过敏反应后血清IgE抗体和纤维蛋白溶酶增加，并维持较长时间。
Is there any association between asthma and drug allergy?
The rate of allergic asthma has been increasing during the past few years. A recent New England Journal of Medicine review article of allergy and allergic diseases included asthma and anaphylaxis as two different allergic diseases (1,2). Most patients with asthma are atopic. Atopy describes IgE mediated diseases, and patients with atopy are more likely to have a drug allergy, and to experience an anaphylactic episode. There are also reports of treatment of allergic asthma with monoclonal anti-IgE antibody, further demonstrating that allergic asthma is mediated, at least in part, by IgE antibodies (3).
What do you make out of the difficulty trying to ventilate her during a prior anesthetic?
Her description implies that she developed bronchoconstriction during her last anesthetic. However, patients are often inaccurate in their relaying of information, and a review of the anesthetic record is imperative. Assuming that she actually had an episode of bronchospasm, it may be difficult to differentiate between anaphylaxis and an acute asthmatic attack. Asthma is a disease characterized by airway hyperreactivity to nonspecific stimuli. Stimuli such as the endotracheal tube may cause bronchoconstriction. Anaphylaxis, as discussed earlier in the week, may also present with bronchoconstriction. The release of mediators from tissue mast cells and circulating basophils, upon presentation of the antigen, is responsible for the clinical presentation of anaphylaxis. These mediators include histamine, which increases bronchial smooth muscle contraction, and neutral proteases such as tryptase, which decrease the bronchodilatory activity of neuropeptides inducing bronchoconstriction.
Nonspecific nonimmunologic histamine release may also cause bronchospasm. This patient probably has a high baseline IgE, and medications such as some muscle relaxants and morphine may cause histamine release. This may result in bronchial smooth muscle contraction. Opioid allergy is extremely rare. This patient probably has nonspecific histamine release in response to opioids. It may be helpful to clarify what she means by allergy, as some patients describe side effects, such as nausea and vomiting.
Although less likely, other causes of bronchoconstriction should also be considered and include right mainstem obstruction, inadequate anesthesia, pneumothorax, mechanical obstruction, endobronchial intubation, pulmonary aspiration, pulmonary edema and pulmonary embolism (4).
How do you differentiate between bronchoconstriction from asthma and anaphylaxis?
It may be difficult to differentiate bronchoconstriction from asthma and anaphylaxis, as bronchospasm may be the only presenting sign of anaphylaxis. It may occur after the administration of a medication or latex exposure at the time of induction of anesthesia. Other presenting signs such as angioedema, generalized urticaria and cardiovascular collapse would suggest anaphylaxis. The timing of the bronchospasm and the placement of the endotracheal tube (ETT) may also be helpful. Although presentation immediately after the placement of the endotracheal tube is more likely to be an acute asthmatic attack, anaphylaxis cannot be ruled out (4). Development of bronchospasm not related to the placement of the ETT is more likely to suggest anaphylaxis, especially if a new medication was recently given.
A serum tryptase and antigen-specific IgE antibodies may aid in the diagnosis. Serum IgE antibody and tryptase are increased following an anaphylactic reaction, and remain elevated hours after the event.
Question Author: David Hepner, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School
References:
1. Kay AB. Allergy and allergic diseases. First of two parts. N Engl J Med 2001;344:30-37.
2. Kay AB. Allergy and allergic diseases. Second of two parts. N Engl J Med 2001;344:109-13.
3. Milgrom, H, Fick RB, Su J, Reimann J, Bush RK, Watrous ML, Metzger WJ. Treatment of allergic asthma with monoclonal anti-IgE antibody. N Engl J Med 1999;341:1966-73.
4. Hepner DL. Sudden bronchospasm on intubation: Latex anaphylaxis? J Clin Anesth 2000;162-6.
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