I.

DEFINITION
ANAPHYLACTIC REACTION Anaphylaxis is an acute, potentially life-threatening hypersensitivity reaction, involving the release of mediators from mast cells, basophils and recruited inflammatory cells. Anaphylaxis is defined by a number of signs and symptoms, alone or in combination, which occur within minutes, or up to a few hours, after exposure to a provoking agent. It can be mild, moderate to severe, or severe. Most cases are mild but any anaphylaxis has the potential to become life-threatening. Anaphylaxis develops rapidly, usually reaching peak severity within 5 to 30 minutes, and may, rarely, last for several days. What happens in anaphylaxis? Mast cell leukocyte cytokine cascade. Mast cell activation results in the release of many mediators that include histamine, leukotrienes, tumour necrosis factor and various cytokines. The large numbers of mediators provide redundancy and positive feedback mechanisms whereby other effector cells are recruited to release more mediators, perpetuating the allergic response. This amplification and perpetuation, which has been referred to as a mast cell leukocyte cytokine cascade, underscores the importance of physiological antagonism with adrenaline and fluid resuscitation, rather than antagonism of a single mediator such as histamine.

II. ETIOLOGY
1. IgE-Mediated Reactions Foods In theory, any food glycoprotein is capable of causing an anaphylactic reaction. Foods most frequently implicated in anaphylaxis are: Peanut (a legume) Tree nuts (walnut, hazel nut/filbert, cashew, pistachio nut, Brazil nut, pine nut, almond) Fish Shellfish (shrimp, crab, lobster, oyster, scallops) Milk (cow, goat) Chicken eggs Seeds (cotton seed, sesame, mustard) Fruits, vegetables Food sensitivity can be so severe that a systemic reaction can occur to particle inhalation, such as the odors of cooked fish or the opening of a package of peanuts. Pollen A severe allergy to pollen, for example, ragweed, grass or tree pollen, can indicate that an individual may be susceptible to anaphylaxis or to the oral allergy syndrome (pollen/food syndrome) caused by eating certain plant-derived foods. This is due to homologous allergens found between pollens and foods. The main allergen of all grasses is profilin, which is a pan-allergen, found in many plants, pollens and fruits, and grass-sensitive individuals can sometimes react to many plant-derived foods. Typical aero-allergen food cross-reactivities are: Birch pollen: apple, raw potato, carrot, celery and hazelnut Mugwort pollen: celery, apple, peanut and kiwifruit Ragweed pollen: melons (watermelon, cantaloupe, honeydew) and banana Latex: banana, avocado, kiwifruit, chestnut and papaya

Antibiotics and Other Drugs Penicillin is the most common cause of anaphylaxis, for whatever reason, not just drug-induced cases. Penicillin and other antibiotics are haptens, molecules that are too small to elicit immune responses but which may bind to serum proteins and produce IgE antibodies. Serious reactions to penicillin occur about twice as frequently following intramuscular or intravenous administration versus oral administration, but oral penicillin administration may also induce anaphylaxis. Neither atopy, nor a genetic history of allergic rhinitis, asthma or eczema, is a risk factor for the development of penicillin allergy.

MUSCLE RELAXANTS Muscle relaxants, for example, suxamethonium, alcuronium, vecuronium, pancuronium and atracurium, which are widely used in general anesthesia, account for 70-80% of all allergic reactions occurring during general anesthesia. Reactions are caused by an immediate IgE-mediated hypersensitivity reaction. Insects Hymenoptera venoms (bee, wasp, yellow-jacket, hornet, fire ant) contain enzymes such as phospholipases and hyaluronidases and other proteins which can elicit an IgE antibody response. Latex Latex is a milky sap produced by the rubber tree Hevea brasiliensis. Latexrelated allergic reactions can complicate medical procedures, for example, internal examinations, surgery, and catheterization. Medical and dental staff may develop occupational allergy through use of latex gloves. Miscellaneous Examples of miscellaneous agents which cause anaphylaxis are insulin, seminal proteins, and horse-derived antitoxins, the latter of which are used to neutralize venom in snake bites. Individuals who have IgA deficiency may become sensitized to the IgA provided in blood products. Those selective IgA deficient subjects (1:500 of the general population) can develop anaphylaxis when given blood products, because of their anti-IgA antibodies (probably IgE-anti-IgA). 2. Cytoxic and Immune Complex Complement-Mediated Reactions Anaphylactic responses have been observed after the administration of whole blood or its products, including serum, plasma, fractionated serum products and immunoglobulins. One of the mechanisms responsible for these reactions is the formation of antigen-antibody reactions on the red blood cell surface or from immune complexes resulting in the activation of complement. The active byproducts generated by complement activation (anaphylatoxins C3a, C4a and C5a) cause mast cell (and basophil) degranulation, mediator release and generation, and anaphylaxis. In addition, complement products may directly induce vascular permeability and contract smooth muscle. Cytotoxic reactions can also cause anaphylaxis, via complement activation. Antibodies (IgG and IgM) against red blood cells, as occurs in a mismatched blood transfusion reaction, activate complement. This reaction causes agglutination and lysis of red blood cells and perturbation of mast cells resulting in anaphylaxis. 3. Non-immunologic Mast Cell Activators Radiocontrast Media, Low-molecular Weight Chemicals Mast cells may degranulate when exposed to low-molecular-weight chemicals. Hyperosmolar iodinated contrast media may cause mast cell degranulation by

activation of the complement and coagulation systems. These reactions can also occur, but much less commonly, with the newer contrast media agents. Narcotics Narcotics are mast cell activators capable of causing elevated plasma histamine levels and non-allergic anaphylaxis. They are most commonly observed by anesthesiologists. 4. Modulators of Arachidonic Acid Metabolism Aspirin, Ibuprofen, Indomethacin and other Non-steroidal Anti-inflammatory Agents (NSAIDs) IgE antibodies against aspirin and other NSAIDs have not been identified. Affected individuals tolerate choline or sodium salicylates, substances closely structurally related to aspirin but different in that they lack the acetyl group. 5. Sulfiting Agents Sodium and Potassium Sulfites, Bisulfites, Metabisulfites, and Gaseous Sulfur Dioxides These preservatives are added to foods and drinks to prevent discoloration and are also used as preservatives in some medications. Sulfites are converted in the acid environment of the stomach to SO2 and H2SO3, which are then inhaled. They can produce asthma and non-allergic hypersensitivity reactions in susceptible individuals. 6. Idiopathic Causes Exercise Exercise alone can cause anaphylaxis as can food-induced anaphylaxis, Exercise-induced anaphylaxis can occur during the pollinating season of plants to which the individual is allergic. Catamenial Anaphylaxis Catamenial anaphylaxis is a syndrome of hypersensitivity induced by endogenous progesterone secretion. Patients may exhibit a cyclic pattern of attacks during the premenstrual part of the cycle.
Flushing, tachycardia, angioedema, upper airway obstruction, urticaria and

other signs and symptoms of anaphylaxis can occur without a recognizable cause. Diagnosis is based primarily on the history and an exhaustive search for causative factors. Serum tryptase and urinary histamine levels may be useful, in particular, to rule out mastocytosis.

III. INCIDENCE
The true incidence of anaphylaxis is not known. Estimated incidence of fatal anaphylaxis is 500 to 1,000 individuals per year in the US, with a reaction to peanuts and tree nuts the most common cause. The risk of an anaphylactic reaction occurring in an individual in the US is 1% to 3%. Although fatal anaphylactic shock is rare, milder forms occur more frequently. Food allergies are present in 2.5% of adults and 6% to 8% of children, although by age 10 many children outgrow allergies to milk and eggs. Anaphylaxis occurs at a rate of 50 to 2,000 episodes per 100,000 people in the U.S. Anaphylaxis causes approximately 1500 deaths in the U.S. annually. A majority of anaphylaxis victims have pre-existing allergies.

 The cause of anaphylaxis is unidentified in one-third to two-thirds of patients.

There were 1.03 million allergy-related emergency department visits each year from 1993 to 2004.

IV. CLINICAL MANIFESTATION

Anaphylaxis is a severe reaction that affects multiple areas of the body. The severity of the reaction varies from person to person. Subsequent reactions to the same trigger are typically similar in nature. The more rapid the onset of symptoms, the more severe the reaction is likely to be. A history of allergic disease (rhinitis,eczema, asthma) does not increase the risk of developing IgE mediated anaphylaxis, but it does incline the person to a nonIgE-mediated reaction. Underlying asthma may result in a more severe reaction and can be more difficult to treat. The risk of anaphylaxis may diminish over time if there are no repeated exposures or reactions. However, a person at risk should always expect the worst and be prepared. The symptoms of an anaphylactic reaction may occur within seconds of exposure or be delayed 15 to 30 minutes, or even an hour or more after exposure (typical of reactions to aspirin and similar drugs). Early symptoms are often related to the skin and include: - flushing (warmth and redness of the skin) - Itching (often in the groin or armpits) - hives. These symptoms are often accompanied by - a feeling of "impending doom - anxiety - sometimes a rapid, irregular pulse Frequently following the above symptoms, throat and tongue swelling results in hoarseness, difficulty swallowing, and difficulty breathing. Symptoms of rhinitis (hay fever) or asthma may occur, causing a runny nose; sneezing, and wheezing, which may worsen the breathing difficulty; vomiting, diarrhea, and stomach cramps may develop. About 25% of the time, the mediators flooding the bloodstream cause a generalized opening of capillaries (tiny blood vessels) which results in a drop in blood pressure, lightheadedness, even loss of consciousness. These are the typical features of anaphylactic shock.

V. DIAGNOSTIC PROCEDURE/EXAMINATION
1. Patch Test is a method used to determine if a specific substance causes allergic inflammation of the skin. Any individual with eczema suspected of having allergic contact dermatitis and/or atopic dermatitis needs patch testing. Interpretation of the results Negative (-) Irritant reaction (IR) Equivocal / uncertain (+/-) Weak positive (+)

 Strong positive (++) Extreme Reaction Negative (-) no skin changes in the tested area. Irritant reaction (IR) Irritant reactions include miliaria (sweat rash), follicular pustules and burn-like reactions, inflammation sharply limited to the exposed area, lack of infiltrate, small petechiae and efflorescences other than papules and vesicles Weak positive (+) Weak positives are slightly elevated pink or red plaques, usually with mild vesiculation, palpable erythema - moderate edema or infiltrate, papules not present or scarce, vesicles not present. Strong positive (++) Strong positives are papulovesicles and extreme reactions have spreading redness, severe itching and blisters or ulcers. Equivocal / uncertain (+/-) faint, non-palpable erythema Extreme Reaction (+++) coalescing vesicles, bullae or ulceration 2. Serum Tryptase Test is the most abundant secretory granule-derived serine proteinase contained in mast cells that has been used as a marker for mast cell activation. Serum levels are normally less than 11.4 ug/mL. Elevated levels of serum tryptase occur in both anaphylactic and anaphylactoid reactions, but a negative test does not exclude anaphylaxis. Tryptase levels of 11.5 g/L or more indicate either activation of mast cells (as in an anaphylactic or allergic reaction) or increased total mast cell levels (as in mastocytosis). Serum-separator tube Enipuncture is used for specimen collection, and a red-top tube (preferable) or a serum gel separator tube (see the image below) is used. Collection of the sample should take place 15 minutes to 3 hours after onset of allergy symptoms. The serum or plasma (results are compatible with each other) is then separated with centrifugation or via clotting in a gel separator tube. At least 0.2-0.5 mL of serum is required, meaning that at least 0.5-1 mL of blood needs to be collected. Mild hemolysis, lipemia, and icterus in the sample are acceptable. > Also known as: Mast cell tryptase; Alpha tryptase; Beta tryptase; Mature tryptase Formal name: Total Tryptase. > The tryptase test is a useful indicator of mast cell activation. It may be ordered to confirm a diagnosis of anaphylaxis and to help diagnose mastocytosis. Interpretation of the results When both total tryptase and mature (essentially beta) tryptase tests are performed and compared, ratios of total-to-mature tryptase that are <10 are suggestive of anaphylaxis, while ratios >20 are suggestive of systemic mastocytosis. Normal tryptase results may indicate that a person's symptoms are due to another cause or may be a matter of sample timing. Acutely elevated tryptase levels in a person with symptoms of anaphylaxis indicate it as the likely diagnosis. 3. Allergy Blood Testing

 Also known as: RAST Test; Radioallergosorbent Test; Allergy Screen Formal name: Allergen-specific IgE Antibody Test This test measures the amount of allergen-specific immunoglobulin E (IgE) in the blood in order to detect an allergy to a particular substance. IgE is a protein associated with allergic reactions; it is normally found in very small amounts in the blood. When to Get Tested.. When you have symptoms such as hives, dermatitis, nasal congestion, red itchy eyes, asthma, or abdominal pain that your doctor suspects may be caused by an allergy. Sample Required.. A blood sample drawn from a vein in your arm. Interpretation of the results > Negative results indicate that a person probably does not have a "true allergy," an IgE-mediated response to that specific allergen, but the results of allergen-specific IgE antibody tests must always be interpreted and used with caution and the advice of the doctor. > Elevated results usually indicate an allergy, but even if the specific IgE test is positive, a person may or may not ever have an actual physical allergic reaction when exposed to that substance. RAST (Blood Test) Results RAST TESTS have been reported as CLASS 0 to CLASS 5 or 6. Class 0 indicates no allergy. Class 5 or 6 indicates high allergy. CLASS 0 (less than 0.35 KU/L) CLASS 1 (0.35-0.7 KU/L) CLASS 2 (0.71-3.5 KU/L) CLASS 3 (3.51-17.5 KU/L) CLASS 4 (17.51-50 KU/L) CLASS 5 (50.01-100 KU/L) CLASS 6 (greater than 100 KU/L) VI. Medical/Pharmacological Management. Acute management of anaphylaxis includes the following: Place the patient in the supine position (or left lateral position for vomiting patients); Give intramuscular adrenaline; Resuscitate with intravenous saline (20 mL/kg body weight, repeated up to a total of 50 mL/kg over the first half hour); Support the airway and ventilation; Give supplementary oxygen. Intramuscular 1 : 1000 (1 mg/mL) adrenaline at a dose of 0.01 mg/kg (0.01 mL/kg) body weight up to a maximum dose of 0.5 mg (0.5 mL) injected into the lateral thigh (vastus lateralis) has the advantage that it can be given without delay, is absorbed more reliably than injections into other locations or subcutaneously, is anecdotally effective in most cases when given early, and avoids the potentially lethal effects of large intravenous bolus injections. The appropriate dose of EpiPen (CSL Limited, Melbourne, VIC) can be used instead, if available. The intramuscular dose can be repeated after 35 minutes if required. Intravenous adrenaline If resuscitation using intramuscular adrenaline and volume expansion with intravenous saline is ineffective, an infusion of intravenous adrenaline may be required, but this should be done only by experienced hands. Intravenous boluses of adrenaline are potentially dangerous and should not be used unless cardiac arrest is

imminent. Controlled intravenous infusions of adrenaline were shown to be safe and effective in one prospective Australian study. Management of persistent airway tract obstruction and/or hypotension If the patient is still unresponsive after the treatments outlined above, there are several further options: Persistent bronchospasm may respond to treatment with additional bronchodilators. If intubation is required, continuous puffs of salbutamol through an aerosol port directly into the ventilation circuit may help to break severe bronchospasm. Persistent stridor may respond to continuous nebulised adrenaline (5 mg in 5 mL [ie, five 1 mg ampoules]) in addition to parenteral adrenaline. Surgical airway intervention (cricothyrotomy) may be required. Persistent hypotension may be due to either profound vasodilation or cardiac failure. Anecdotally, vasodilation may respond to vasopressors such as metaraminol or vasopressin. In patients who have pre-existing heart failure or are taking -blockers, a phosphodiesterase inhibitor such as glucagon may be tried. Epinephrine Generic Name: Epinephrine Brand Name: Adrenalin Chloride, Epinephrine Classification: Autonomic Nervous System Agent; Alpha and Beta Adrenergic Agents; Bronchodilator Rationale: to reverse the life-threatening symptoms of anaphylactic shock if given in time. to rapidly reverse the uncomfortable flushing and itching that accompanies most anaphylactic reactions Benadryl Generic Name: Diphenhydramine Brand Name: Benadryl Classification: Anti-allergic Rationale: to decrease allergic response Ranitidine Generic Name: Ranitidine Hydrochloride Brand Name: Zantac Classification: Anti-histamine Rationale: to decrease allergic response

VII. NURSING MANAGEMENT

Primary nursing diagnosis: Ineffective airway clearance related to laryngeal edema and bronchospasm. Assessment and Intervention: Obtain information about any recent food intake, medication ingestion, outdoor activities and exposure to insects, or known allergies. Symptoms usually begin within 5 to 30 minutes, and the earlier the signs and symptoms begin, the more severe the reaction. Often the signs and symptoms begin with skin and respiratory involvement and include Ask the members about a family history of drug allergies or a history of previous reactions. Note any hives, which appear as well-defined areas of redness with raised borders and blanched centers. Generalized symptoms include flushing, tingling, and angioedema around the mouth, tongue, eyes, and hands. Wheezing, stridor, loss of the voice, and difficulty breathing indicate laryngeal edema

and bronchospasm and may indicate the need for emergency intubation. Auscultate the patients blood pressure with a high suspicion for hypotension. Auscultate the patients heart to identify cardiac dysrhythmias, which may precipitate vascular collapse. Palpate the patients extremities for signs of cardiovascular compromise, such as weak peripheral pulses and delayed capillary refill. The patient who is experiencing an anaphylactic reaction is often panicky and fearful. Although alert, the patient may express a feeling of helplessness, loss of control, and impending doom. In addition, the family, parents, or significant others are apt to be fearful and severely anxious. Treatment Plan and Intervention: The plan of care depends on the severity of the reaction. Discontinue the administration of any possible allergen immediately. Consider applying a tourniquet to the extremity with the antigen source; this procedure can retard antigen exposure to the systemic circulation but the tourniquet needs to be released every 5 minutes, and it should not be left in place longer than 30 minute. Complete an assessment of the patients airway to ensure patency and adequate breathing. If the patient has airway compromise, endotracheal intubation and mechanical ventilation with oxygenation may be necessary. More severe or prolonged cases of anaphylactic shock are aggressively treated with the establishment of IV access and infusion of normal saline or lactated Ringers as well as supplemental oxygen therapy. The patient may require urinary catheterization to monitor urinary output during periods of instability. The most important priority for nurses is to ensure adequacy of the airway, breathing, and circulation. Keep intubation equipment available for immediate use. Insert an oral or nasal airway if the patient is at risk for airway occlusion but has adequate breathing. Use an oral airway for unresponsive patients and a nasal airway for patients who are responsive. If endotracheal intubation is necessary, secure the tube firmly and suction the patient as needed to maintain the airway. If the patient has a compromised circulation that does not respond to pharmacologic intervention, begin cardiopulmonary resuscitation with chest compressions. Teach the patient and family how to prevent future allergic reactions. Explain the nature of the allergy, the signs and symptoms to expect, and measures to perform if the patient is exposed to the allergen. Teach the patient that if shortness of breath, difficulty swallowing, or the formation of the lump in the throat occurs, she or he should go to an emergency department immediately. If the allergen is a medication, make sure the patient and family understand that they must avoid the various sources of the medication in both prescription drugs and available overthe- counter preparations for the rest of their lives. Encourage the patient to notify all healthcare providers of the allergy prior to treatment. Discharge Guidelines: Provide a complete explanation of all allergic responses and how to avoid future reactions. If the patient has a reaction to a food or medication, instruct the patient and family about the substance itself and all potential sources. If the patient has a food allergy, you may need to include a dietitian in the patient teaching. Encourage the patient to carry an anaphylaxis kit with epinephrine. Teach the patient to administer subcutaneous epinephrine in case of emergencies. Encourage the patient to wear an identification bracelet at all times that specifies the allergy.

VIII. COMPLICATION
Complications of Anaphylaxis are secondary conditions, symptoms, or other disorders that are caused by Anaphylaxis. In many cases the distinction between symptoms of Anaphylaxis and complications of Anaphylaxis is unclear or arbitrary. The list of complications that have been mentioned in various sources for Anaphylaxis includes: Hypotension: Blood pressure that is too low. Syncope: Syncope is the temporary loss of consciousness due to a sudden decline in blood flow to the brain. Shock: Severe condition from reduced blood circulation. Heart failure: is a very serious condition in which the heart muscle has been damaged. Heart attack, also called myocardial infarction, is a very serious condition in which the heart is not receiving enough oxygen to function properly. Heart attack is a common cause of death. Tissue swelling: A condition which is characterized by the swelling of tissues of the body. Complications and sequelae of Anaphylaxis from the Diseases Database include: Pulmonary oedema Breathlessness Bronchospasm Shock Cardiac arrest Urticaria Acute lung syndrome Stridor