Review and Feature Article
Current Knowledge and Management of Hypersensitivity to Perioperative Drugs and Radiocontrast Media

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Perioperative anaphylaxis is an iatrogenic clinical condition, most often after anesthetic induction. Several mechanisms are implicated, including IgE- and non–IgE-mediated mechanisms. Perioperative anaphylaxis tends to be severe and has a higher mortality rate than anaphylaxis in other settings. This is partly due to factors that impair early recognition of anaphylaxis. Neuromuscular blocking agents, latex containing products, and antibiotics are the most common etiology. Chlorhexidine and dyes are increasingly culprits. The newest emerging cause is sugammadex, which is used for reversal of the effects of steroidal neuromusclar agents, such as rocuronium. Latex-induced allergy is becoming less common than in the 1980s due to primary and secondary prevention measures. Serum tryptase levels during the time of anaphylaxis and skin testing to suspected agents as an outpatient are necessary to confirm the diagnosis. Management includes epinephrine and aggressive fluid therapy. With radiocontrast media allergy, patients with a history of immediate hypersensitivity reactions to radiocontrast media should receive steroid and antihistamine premedication before re-exposure. Because IgE-mediated anaphylaxis to radiocontrast media is rare, there is a universal consensus that routinely skin testing all patients with a past reaction is not effective.

Section snippets

Epidemiology of Perioperative Anaphylaxis

The incidence of anaphylaxis during general anesthesia is approximately 1:2,000 to 1:20,000 from different countries.1, 2, 3, 4, 5, 6, 7, 8 The variability in estimates of incidence and prevalence reflects difficulties in determining the total number of anesthesia cases. Perioperative anaphylaxis occurs equally in girls and boys. It is more common in adult women compared with men. The proportion of IgE-mediated allergic reactions seems to be similar between countries, around 60% of all allergic

Etiologies of Perioperative Anaphylaxis

Penicillins and cephalosporins account for most perioperative cases of anaphylaxis in the United States.8, 9, 13 Those patients with IgE-mediated allergy to penicillins may be reactive to the beta-lactam ring structure that is common to all penicillins, except in the case of amoxicillin, where the likely culprit is the side chain. In the United States, most penicillin-allergic patients are sensitive to the beta-lactam core. It has been stated that the risk of cephalosporin cross-sensitivity in

Clinical Presentation of Perioperative Anaphylaxis

Perioperative anaphylaxis usually occurs within minutes of anesthetic induction. Cardiovascular and respiratory compromise are the hallmarks of perioperative anaphylaxis.44 Cardiovascular collapse may be the first detected manifestation in up to 50% of the cases.13 Cutaneous symptoms may be absent or may not be visible due to surgical drapes. Typically, the initial diagnosis is based on the timing of the suspected trigger and the onset of clinical symptoms.

The clinical diagnosis is presumptive.

Mechanisms

Anaphylaxis is an acute, potentially fatal syndrome affecting multiple organs, resulting from the sudden release of mast-cell and basophil-derived mediators into the circulation.53 The mechanisms include IgE-dependent mechanisms, non–IgE-mediated immunologic mechanisms (previously called anaphylactoid), and direct release of histamine and other mediators from mast cells and basophils, complement activation, and kallikrein activation. Non–IgE-mediated anaphylaxis can clinically present like an

Management

One of the cornerstones in the treatment of perioperative anaphylaxis is aggressive fluid therapy. Fluid therapy is required to compensate for the peripheral vasodilation and the strong interstitial capillary leakage that occurs during anaphylaxis. The best treatment for the paradoxical bradycardia is fluid therapy. It would be dangerous to give an anticholinergic, as this bradycardia is an adaptive life-saving mechanism to allow the ventricles to fill. There is no randomized study comparing

Testing

The evaluation usually starts with reviewing the clinical history, anesthesia records, nursing records, and operative/procedural reports. Skin testing remains the best way to identify the likely agent and also help provide alternative drugs. Skin testing is more sensitive than in vitro testing, in most cases.

A total serum tryptase concentration can be measured between 1 and 4 hours after the event. It typically reaches a peak within 15 and 120 minutes. Tryptase's half-life is 120 minutes and

Options for Retreatment

Patients with IgE-mediated reactions to antibiotics are generally managed by avoiding the culprit antibiotic and an alternative antibiotic is used. Vancomycin reactions are rarely IgE mediated and can be given with antihistamine premedication and slower rates of infusion.

For patients with a reaction to NMBA, it is recommended to use an alternative agent. We often will skin test to at least a couple of NMBA alternatives and use one that was skin test negative. Desensitization to NMBA is not

Conclusions

Perioperative anaphylaxis is rare, but can be fatal. It is usually rapid and with an unexpected onset in the operating room. Fluid resuscitation and epinephrine are key to treatment. Drawing a serum tryptase is recommended to confirm anaphylaxis. Allergy investigations to identify the culprit are important, so the patient can undergo the needed procedure. In the United States, antibiotics are the most common etiology. In Europe, anaphylaxis to NMBAs is common. Chlorhexidine and blue dye allergy

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    No funding was received for this work.

    Conflicts of interest: K. S. Hsu Blatman is employed by the Brigham and Women's Hospital. D. L. Hepner serves as an editor for UpToDate.

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