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

This week we conclude our discussion of anaphylaxis, and will discuss the treatment of an anaphylactic episode during an anesthetic.

You are in the middle of the anesthetic for a total colectomy when you notice that the patient's skin is red and blotchy and his blood pressure is 85/40 (it was 110-120s/50-60s throughout most of the procedure). There are no other hemodynamic changes and there has not been any major change in what the surgeons are doing.

1.  What is the likelihood that this is an episode of anaphylaxis?

2.  How do you treat an episode of intraoperative anaphylaxis?

3.  What would you tell this patient after he is recovered and conscious?

4.  Is there any role for premedication prior to a future anesthetic?

过敏反应的病理生理，过敏反应与类过敏反应的区别及其治疗：

我们对过敏反应的讨论进行总结，并讨论麻醉中偶发过敏反应的处理。

全结肠切除术麻醉中发现患者皮肤出现发红并有斑片状改变，血压为85/40mmHg（术中大多数时间内维持在110-120/50-60 mmHg），没有其它血流动力学变化，也没有外科重大操作。

1、  该过敏反应的可能原因是什么？

2、  如何治疗该手术中出现的过敏反应？

3、  在患者苏醒后如何告知患者？

4、  麻醉之前使用术前用药是否有用？

参考答案：

1、  该过敏反应的可能原因是什么？

注意当时是否应用了某些药物或制剂非常重要，尤其是当首次使用时更应注意。多数情况下，相对于新开发或近期刚引进的药物，常规药物或制剂如血制品或通过麻醉药给与的橡胶（编者注：如各种溶剂）等很少导致过敏反应[1]。如果这确实属于过敏，麻醉医生英觉得自己很“幸运”，因为这时过敏的一些早期症状很明确。麻醉期间的过敏反应的诊断极富挑战性，因为患者躯体的大部分在手术单下，无法看到，同时麻醉药物本身有时可出现与过敏早期症状类似的表现。麻醉期间经常会出现过敏反应的唯一表现是严重的支气管痉挛或突然的心血管性虚脱。

麻醉期间非特异性、非免疫性组胺释放也比过敏反应的几率高，常出现在使用吗啡或某些肌肉松弛剂时。考虑该患者的症状与组胺释放有关，但很难区分是免疫性或非免疫性组胺释放。

2、  如何治疗该手术中出现的过敏反应？

首先应停止使用可能导致过敏的制剂或麻醉剂。增加吸入氧浓度到100%，并开始静脉输液。过敏指南推荐皮下或肌肉注射肾上腺素0.2～0.5mg[2]，但静脉注射的出现和麻醉期间过敏反应的严重程度提示，静脉注射更有效。肾上腺素以5～10 mcg的梯度增加，除非出现严重的低血压或心血管性虚脱[3]。心血管性虚脱时推荐剂量0.1～0.5mg静脉注射[3]。同时使用其它药物如抗组胺药（0.5～1 mg/kg苯海拉明）、注射肾上腺素维持血压（5～10 mcg/min）、支气管扩张剂（沙丁胺醇、异丙阿托品喷雾剂）[3]。
虽然认为皮质激素不能迅速发挥效应，但仍应使用，因为其可抑制过敏反应几小时后出现的炎症细胞浸润。

3、  在患者苏醒后如何告知患者？

应尽可能的明确致敏剂。检测血清纤维蛋白溶酶以确认过敏反应，同时检测制剂特异性IgE抗体。通过皮内试验确定诊断。患者应佩戴识别其过敏物质的腕带，应随时随身携带Epi-pen，并告知其保健医生自己的药物过敏史。

4、  麻醉之前使用术前用药是否有用？

术前使用H1、H2阻滞剂和类固醇，对预防放射性造影剂的反应有一定效果，但这些反应并非IgE介导[4]。尚没有证据表明术前给药可预防IgE介导的过敏反应发生，并且这些药物的使用实质上可掩盖过敏的早期症状，导致发生过敏时只有一种表现。

What is the likelihood that this is an episode of anaphylaxis?

It is important to notice if there was any medication or agent that was recently administered, especially if it was the first time that it was given. For the most part, medications or agents such as blood products or latex that have been given throughout the anesthetic are less likely to cause an allergic reaction than agents that were recently introduced (1). If this is indeed an allergic reaction, the anesthesiologist should consider him/herself "lucky", as some of the early presenting signs of anaphylaxis are manifested here. The diagnosis of anaphylaxis during an anesthetic is often challenging as most of the body is covered by drapes, and the anesthetic itself may sometimes mimic early signs of anaphylaxis. Frequently, the only sign of anaphylaxis during an anesthetic is severe bronchospasm or sudden cardiovascular collapse.

Nonspecific, nonimmunologic histamine release is also far more frequent than anaphylaxis and is common with medications such as morphine and certain muscle relaxants. While the symptoms of this patient are consistent with histamine release, it may be difficult to differentiate between immunologic and nonimmunologic histamine release.

How do you treat an episode of intraoperative anaphylaxis?

The first line of action ought to be to discontinue the potential causative agent and the anesthetic. The inspired oxygen should be increased to 100% with potential airway support, and intravenous fluid replacement should be commenced. While the Allergy literature recommends 0.2-0.5 mg epinephrine subcutaneously or intramuscularly (2), the presence of an intravenous and the severity of anaphylaxis during an anesthetic suggest that an intravenous approach is more effective. Epinephrine should be given in 5-10 mcg increments unless severe hypotension or cardiovascular collapse is present (3). Doses of 0.1-0.5 mg IV have been recommended in cases of cardiovascular collapse (3). Other medications that should be given include antihistamines (0.5-1 mg/kg diphenhydramine), epinephrine infusion to support the blood pressure (epinephrine 5-10 mcg/min) and bronchodilators (albuterol and ipratropium bromide nebulizers) (3).

Although corticosteroids should not be expected to provide any immediate benefit, they should be given as they may help to decrease the swelling and inflammation that often accompany anaphylaxis hours after its initial presentation.

What would you tell this patient after he is recovered and conscious?

An attempt should be made to diagnose the causative agent. Serum tryptase should be drawn to confirm that the episode represented true anaphylaxis and agent-specific IgE antibodies should also be obtained. Definitive diagnosis is made with the use of intradermal skin tests. The patient should wear a bracelet that identifies what he is allergic to, should carry an Epi-pen at all times, and should inform healthcare providers about his drug allergy.

Is there any role for premedication prior to a future anesthetic?

Premedication with H1 blockers, H2 blockers and steroids, has a role for reactions to radiocontrast media, but these reactions are not IgE mediated (4). There is no evidence to support the use of premedication to prevent IgE mediated anaphylaxis, and their use may actually mask the early signs of anaphylaxis, leaving a full blown episode as the first and only presentation.

References:

1.  Weiss ME, Adkinson Jr NF, Hirshman CA. Evaluation of allergic drug reactions in the perioperative period. Anesthesiology 1989;71:483-86.
2.  Grupe S. Algorithm for the treatment of acute anaphylaxis. J Allergy Clin Immunol 1998;101:S469-471.
3.  Levy JH. Allergy and adverse drug reactions. American Society of Anesthesiologists Annual Meeting Refresher course Lectures 2000;162:1-7.
4.  Weiss ME. Drug allergy. The Medical Clinics Of North America 1992;76:857-82.


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