Which emergency care actions are priority for a hospitalized client who develops an anaphylactic reaction after receiving an intravenous medication?

IgE-mediated anaphylaxis is the classic form of anaphylaxis, whereby a sensitizing antigen elicits an IgE antibody response in a susceptible individual. The antigen-specific IgE antibodies then bind to mast cells and basophils. Subsequent exposure to the sensitizing antigen causes cross-linking of cell-bound IgE, resulting in mast cell (and/or basophil) degranulation.

Other types of immunologic anaphylaxis do not involve IgE. For example, anaphylaxis resulting from administration of blood products, including intravenous immunoglobulin, or animal antiserum is due, at least in part, to complement activation. Immune complexes formed in vivo or in vitro can activate the complement cascade. Certain byproducts of the cascade—plasma-activated complement 3 (C3a), plasma-activated complement 4 (C4a), and plasma-activated complement 5 (C5a)—are called anaphylatoxins and can cause mast cell/basophil degranulation.

When mast cells and basophils degranulate, whether by IgE- or non–IgE-mediated mechanisms, preformed histamine and newly generated leukotrienes, prostaglandins, and platelet-activating factor (PAF) are released. In the classic form, mediator release occurs when the antigen (allergen) binds to antigen-specific IgE attached to previously sensitized basophils and mast cells. The mediators are released almost immediately when the antigen binds.

Certain agents are thought to cause direct nonimmunologic release of mediators from mast cells, a process not mediated by IgE. These include opioids, dextrans, protamine, and vancomycin. Mechanisms underlying these reactions are poorly understood but may involve specific receptors (eg, opioids) or non–receptor-mediated mast cell activation (eg, hyperosmolarity).

Inciting agents

The most common inciting agents in anaphylaxis are foods, Hymenoptera stings, and intravenous (IV) contrast materials. Anaphylaxis may also be idiopathic.

Immunologic IgE-mediated reactions

Typical examples of IgE-mediated anaphylaxis include the reactions to many foods, drugs, and insect stings.

Hypersensitivity to foods is a problem encountered throughout the industrialized world. [8] In the United States, an estimated 4 million Americans have well-substantiated food allergies. A study from Australia showed that more than 10% of 12-month-old children had challenge-proven IgE-mediated food allergies. [9] In Montreal, 1.5% of early elementary school students were found to be sensitized to peanuts. Reactions to foods are thought to be the most common prehospital (outpatient) cause of anaphylaxis.

Certain foods are more likely than others to elicit an IgE antibody response and lead to anaphylaxis. Foods likely to elicit an IgE antibody response in all age groups include peanuts, tree nuts, fish, and shellfish. Those likely to elicit an IgE antibody response in children also include cow’s milk, eggs, wheat, and soy.

An analysis of 32 fatalities thought to be due to food-induced anaphylaxis revealed that peanuts likely were the responsible food in 62% of the cases. In placebo-controlled food challenges, peanut-sensitive patients can react to as little as 100 µg of peanut protein. [10] The Rochester Epidemiology Project, in agreement with earlier studies, found that food ingestion was the leading cause of anaphylaxis, accounting for as many as one third of all cases. [11]

In the past, a history of IgE-mediated egg allergy has been a contraindication to receiving the annual influenza vaccination. A few years ago, egg-allergic individuals received influenza vaccination, but typically with a graded multi-dose protocol or based on skin prick testing to the vaccine itself. Given a dearth of recent evidence that egg-allergic individuals can safely receive the influenza vaccine with no increased risk of systemic reaction as compared to the general population, the most recent guidelines now recommend that all egg-allergic individuals should be vaccinated with a single dose of influenza vaccine. Furthermore, skin testing has no role because no evidence suggests this reliably identifies individuals at risk of a systemic reaction. [12, 13]

Scombroid fish poisoning can occasionally mimic food-induced anaphylaxis. Bacteria in spoiled fish produce enzymes capable of decarboxylating histidine to produce biogenic amines, including histamine and cis-urocanic acid, which is also capable of mast cell degranulation.

Most cases of IgE-mediated drug anaphylaxis in the United States are due to penicillin and other beta-lactam antibiotics. Approximately 1 in 5000 exposures to a parenteral dose of a penicillin or cephalosporin antibiotic causes anaphylaxis.

Penicillin is metabolized to a major determinant, benzylpenicilloyl, and multiple minor determinants. Penicillin and its metabolites are haptens, small molecules that only elicit an immune response when conjugated with carrier proteins. Other beta-lactam antibiotics may cross-react with penicillins or may have unique structures that also act as haptens.

Reactions to cephalosporins may occur in penicillin-allergic patients. In these patients, older agents such as cephalothin, cephalexin, cefadroxil, and cephazolin are more likely to precipitate an allergic reaction than newer agents such as cefprozil, cefuroxime, ceftazidime, or ceftriaxone. This increased reactivity with the older agents is due to greater antigenic similarity of the side chain not present with the newer second- and third-generation agents.

One report suggested that the actual incidence of anaphylaxis to cephalosporins in penicillin-anaphylactic patients is much lower than the 10% frequently quoted—perhaps 1%, with most reactions considered mild. [14] A retrospective study evaluated 606 hospitalized patients with a history of penicillin allergy who were given a cephalosporin. Only one patient (0.17%) had a reaction, and it was minor. [15]

Another paper indicated that patients with a history of allergy to penicillin seem to have a higher risk (by a factor of about 3) of subsequent reaction to any drug and that the risk of an allergic reaction to cephalosporins in patients with a history of penicillin allergy may be up to 8 times as high as the risk in those with no history of penicillin allergy (ie, at least part of the observed “cross-reactivity” may represent a general state of immune hyperresponsiveness, rather than true cross-reactivity). [16]

Pichichero reviewed the complicated literature and offered specific guidance for the use of cephalosporins in patients who have a history of IgE-mediated reactions to penicillin. [17]

Patients with a history of positive skin tests for penicillin allergy are at high risk of subsequent reactions to penicillins. However, approximately 95% of patients with a history of penicillin allergy have negative skin tests and a low risk of reactions. Patients with less well-defined reactions to penicillin have a very low risk (1-2%) of developing anaphylaxis to cephalosporins. The rate of skin-test reactivity to imipenem in patients with a known penicillin allergy is almost 50%. In contrast, no known in vitro or clinical cross-reactivity exists between penicillins and aztreonam.

When either a penicillin or a cephalosporin is the drug of choice for a patient with a life-threatening emergency, a number of options exist. When the history is indefinite, the drug may be administered under close observation; however, when possible, obtain the patient’s informed consent. Immediate treatment measures for anaphylaxis should be available. Alternatively, when the history is more convincing, an alternative agent should be chosen if it provides similar efficacy or one must pursue a desensitization protocol.

Many other drugs have been implicated in IgE-mediated anaphylaxis, albeit less frequently. In the surgical setting, anaphylactic reactions are most often due to muscle relaxants but can also be due to hypnotics, antibiotics, opioids, colloids, and other agents. The prevalence of latex allergy was higher during the 1980s (due to the HIV and hepatitis B and C epidemics and the institution of universal precautions), but the incidence has decreased significantly since the widespread use of latex-free materials. If latex is responsible for anaphylaxis in the perioperative setting, reactions tend to occur during maintenance anesthesia, whereas other agents tend to cause reactions during the induction of anesthesia. Volatile anesthetic agents can cause immune-mediated hepatic toxicity but have not been implicated in anaphylactic reactions. [18]

Hymenoptera stings are a common cause of allergic reaction and anaphylaxis. From 0.5%-3% of the US population experiences a systemic reaction after being stung. [19] In the United States, Hymenoptera envenomations result in fewer than 100 reported deaths per year. Local reaction and urticaria without other manifestations of anaphylaxis are much more common than full-blown anaphylaxis after Hymenoptera stings. Adults with generalized urticaria are at increased risk for anaphylaxis with future stings, but a local reaction, regardless of severity, is not a risk factor for anaphylaxis.

Caution patients treated and released from the emergency department (ED) after an episode of anaphylaxis or generalized urticaria from Hymenoptera envenomation to avoid future exposure when possible. Consider referral to an allergist for desensitization, particularly when further exposure is likely. Additionally, consider prescribing a treatment kit with an epinephrine autoinjector and oral antihistamine. Both are effective measures in preventing or ameliorating future reactions.

Allergen-specific subcutaneous immunotherapy (SCIT) can cause IgE-mediated anaphylaxis. Allergy injections are a common trigger for anaphylaxis. This is not unexpected, because the treatment is based on injecting an allergen to which the patient is sensitive. However, life-threatening reactions are rare. Three studies suggest that fatalities from SCIT occur at a rate of approximately 1 death per 2,500,000 injections. [20, 21, 22] A total of 104 fatalities due to SCIT and skin testing were reported from 1945-2001.

Risk factors for severe anaphylaxis due to immunotherapy include poorly controlled asthma, concurrent use of beta-blockers, high allergen dose, errors in administration, and lack of a sufficient observation period following the injection.

Near-fatal reactions (NFRs) to subcutaneous immunotherapy also have been examined retrospectively. Of 646 allergist-immunologists who responded to a survey on reactions, 273 reported NFRs. The investigators defined an NFR as respiratory compromise, hypotension, or both, requiring emergency epinephrine. Hypotension was reported in 80% and respiratory failure occurred in 10% of NFRs, exclusively in subjects with asthma. Epinephrine was delayed or not administered in 6% of these cases.

Immunologic reactions to aspirin, NSAIDs, and ACE inhibitors

Reactions to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) in the past have been classified as IgE-independent because they were thought to occur from aberrant metabolism of arachidonic acid.

Isolated cutaneous reactions to aspirin/NSAIDs and bronchospasm in aspirin-sensitive asthmatics (often in association with nasal polyposis) are indeed mediated through IgE-independent mechanisms. Blockade of cyclooxygenase by these drugs causes the prostanoid pathway to shut down, resulting in an overproduction of leukotrienes via the 5-lipoxygenase pathway. These patients have marked cross-reactivity between aspirin and most NSAIDs.

Anaphylaxis after taking these drugs, however, apparently occurs via a different mechanism that is more consistent with IgE-mediated anaphylaxis. With true anaphylaxis, the different cyclooxygenase inhibitors do not appear to cross-react. Anaphylaxis occurs only after 2 or more exposures to the implicated drug, suggesting a need for prior sensitization. Finally, patients with true anaphylaxis do not usually have underlying asthma, nasal polyposis, or urticaria.

In one study of nearly 52,000 people taking NSAIDs, 35 developed anaphylactic shock.

Angiotensin-converting enzyme (ACE) inhibitors, widely used in the treatment of hypertension, are associated with angioedema in 0.5-1.0% of patients who take them. Systemic anaphylaxis is rarely associated with these agents.

Immunologic IgE-independent reactions

Anaphylaxis may result from administration of blood products, including IV immunoglobulin, or animal antiserum, at least partly as a consequence of activation of the complement cascade. Certain byproducts of the cascade are capable of causing mast cell/basophil degranulation. (See Pathophysiology.)

Exercise-induced anaphylaxis is a rare syndrome that can take 1 of 2 forms. The first form is food dependent, requiring exercise and the recent ingestion of particular foods (eg, wheat, celery) or medications (eg, NSAIDs) to cause an episode of anaphylaxis. In these patients, exercise alone does not produce an episode, and, similarly, ingesting the culprit food or medication alone does not cause an episode.

The second form is characterized by intermittent episodes of anaphylaxis during exercise, independent of any food ingestion. Anaphylaxis does not necessarily occur during every episode of physical exertion.

Anaphylaxis can be a manifestation of systemic mastocytosis, a disease characterized by excessive mast cell burden in multiple organs. Such patients appear to be at increased risk for food and venom reactions. Alcohol, vancomycin, opioids, radiocontrast media, and other biologic agents that can directly degranulate mast cells are generally discouraged in these patients.

Nonimmunologic reactions

Certain agents, including opioids, dextrans, protamine, and vancomycin, are thought to cause direct, nonimmunologic release of mediators from mast cells. Evidence also exists that dextrans and protamine can activate several inflammatory pathways, including complement, coagulation, and vasoactive (kallikrein-kinin) systems.

Intravenously administered radiocontrast media cause an anaphylactoid reaction that is clinically similar to true anaphylaxis and is treated in the same way. The reaction is not related to prior exposure. Approximately 1-3% of patients who receive hyperosmolar IV contrast experience a reaction. Reactions to radiocontrast media usually are mild (most commonly urticarial), with only rare fatalities reported. Risk of a fatal reaction has been estimated at 0.9 cases per 100,000 exposures.

Pretreatment with antihistamines or corticosteroids and use of low-molecular-weight (LMW) contrast agents lead to lower rates of anaphylactoid reactions to IV radiocontrast media (approximately 0.5%). Consider these measures for patients who have prior history of reaction, since rate of recurrence is estimated at 17-60%. Some institutions use only LMW agents. Personnel, medications, and equipment needed for treatment of allergic reactions always should be available when these agents are administered. Obtain consent before administration.

Patients who are atopic and/or asthmatic also are at increased risk of reaction. In addition, allergic reaction is more difficult to treat in those taking beta-blockers.

Shellfish or iodine allergy is not a contraindication to use of IV contrast and does not mandate a pretreatment regimen. As with any allergic patient, give consideration to use of LMW contrast agents. In fact, the term iodine allergy is a misnomer. Iodine is an essential trace element present throughout the body. No one is allergic to iodine. Patients who report iodine allergy usually have had either a prior contrast reaction, a shellfish allergy, or a contact reaction to povidone-iodine (Betadine).

Mucosal exposure (eg, GI, genitourinary [GU]) to radiocontrast agents has not been reported to cause anaphylaxis; therefore, a history of prior reaction is not a contraindication to GI or GU use of these agents.

Idiopathic anaphylaxis

Idiopathic anaphylaxis is a syndrome of recurrent anaphylaxis for which no consistent triggers can be determined despite an exhaustive search. [23] This recurrent syndrome should be distinguished from a single episode of anaphylaxis for which the etiology may be unclear.

Idiopathic anaphylaxis can be categorized as infrequent (< 6 episodes per year) or frequent (≥6 episodes per year or 2 or more episodes within the last 2 months). [23] One approach is expectant treatment with epinephrine, antihistamines, and prednisone for individuals who have infrequent episodes and a prolonged taper of prednisone for those with frequent episodes.

Most of these patients are female, and atopy appears to be an underlying risk factor. Two thirds of patients have 5 or fewer episodes per year, while one third have more than 5 episodes per year.

A subpopulation of women develops anaphylaxis in relationship to their menstrual cycle; this phenomenon is known as catamenial anaphylaxis. [24, 25] In severe cases, these patients require manipulation of their hormonal levels by medical pituitary suppression and even oophorectomy. Most of these patients react to shifts in progesterone levels, and the diagnosis can be confirmed by provoking an anaphylactic event through administration of low doses of progesterone.

Biphasic and persistent anaphylaxis

The reported incidence of biphasic (recurrent) anaphylaxis varies from less than 1% to a maximum of 23%. Additionally, the reported time of onset of the late phase may vary from 1 to 72 hours (most occur within 8-10 h). Potential risk factors include severity of the initial phase, delayed or suboptimal doses of epinephrine during initial treatment, laryngeal edema or hypotension during the initial phase, delayed onset of symptoms after exposure to the culprit antigen (often a food or insect sting), or prior history of biphasic anaphylaxis. [26]

Persistent anaphylaxis, anaphylaxis that may last from 5-32 hours, occurred in 7 of 25 subjects (28%) in the Stark and Sullivan report, with 2 fatalities. [27] Of 13 subjects analyzed in a report on fatal or near-fatal anaphylaxis to foods, 3 (23%) similarly experienced persistent anaphylaxis. [28] Retrospective data from other investigators, however, suggest that persistent anaphylaxis is uncommon.

Neither biphasic nor persistent anaphylaxis can be predicted from the severity of the initial phase of an anaphylactic reaction. Since life-threatening manifestations of anaphylaxis may recur, it may be necessary to monitor patients 24 hours or more after apparent recovery from the initial phase. [26] When prescribing epinephrine, all patients should be instructed to have 2 injectors on hand at all times.

Risk factors

As mentioned above, atopy is a risk factor for anaphylaxis. In the Rochester Epidemiology Project, 53% of the patients with anaphylaxis had a history of atopic diseases (eg, allergic rhinitis, asthma, atopic dermatitis). [11] The Memphis study detected atopy in 37% of the patients. [29] Other studies have shown atopy to be a risk factor for anaphylaxis from foods, exercise-induced anaphylaxis, idiopathic anaphylaxis, radiocontrast reactions, and latex reactions. Underlying atopy does not appear to be a risk factor for reactions to penicillin or insect stings.

Route and timing of administration affect anaphylactic potential. The oral route of administration is less likely to cause a reaction, and such reactions are usually less severe, although fatal reactions occur following ingestions of foods by someone who is allergic. The longer the interval between exposures, the less likely that an IgE-mediated reaction will recur. This is thought to be due to catabolism and decreased synthesis of allergen-specific IgE over time. This does not appear to be the case for IgE-independent reactions.

A retrospective emergency department study of 302 patients presenting with anaphylaxis, 87 (29%) of whom were taking at least 1 antihypertensive medication, found that antihypertensive pharmacotherapy increased the risk of organ system involvement and hospitalization. [30, 31] There was a more than 2-fold increased risk of involvement in 3 or more organ systems when ACE inhibitors, beta blockers, diuretics, or any antihypertensive medications were used. Most of these agents were also associated with an increased risk for inpatient admission. [30, 31]

What is the standard emergency treatment for an anaphylactic reaction?

When dealing with somebody who has had a suspected anaphylactic reaction What are your treatment priorities?

Which actions would the nurse implement when a client develops an anaphylactic reaction?

How do you treat anaphylaxis in the emergency room?