Postgraduate Medicine

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Anaphylaxis Tommy C. Sim MD To cite this article: Tommy C. Sim MD (1992) Anaphylaxis, Postgraduate Medicine, 92:5, 277-296, DOI: 10.1080/00325481.1992.11701498 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701498

Published online: 17 May 2016.

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Date: 17 July 2016, At: 12:54

~CME credit article

Anaphylaxis How to manage and prevent this medical emergency

Tommy C. Sim, MD

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Preview Patients having a severe anaphylactic reaction must be promptly identified. Airway compromise, significant bronchospasm, or vascular collapse may ensue unless they receive immediate and appropriate medical attention. Follow-up, documentation of details of the reaction, and exhaustive efforts to determine the precipitating factor are also important aspects in the subsequent safety of such patients. Dr Sim addresses all these issues and provides practical treatment and prevention plans.

The clinical syndrome of anaphylactic shock can result from multiple mechanisms and pharmacologic and environmental factors that cause the release ofbiologically active mediators. Classic anaphylaxis is produced by IgEmediated mechanisms, and anaphylactoid reactions are produced by non-IgE-mediated mechanisms. Because the clinical manifestations of IgE-mediated anaphylaxis and non-IgE-mediated anaphylactoid reactions are similar and require identical treatment, this article refers to both types as anaphylaxis. The incidence and prevalence of anaphylaxis vary with the clinical situation (table 1). The elements that predispose to an anaphylactic reaction are not clearly understood. There is no convincing evidence that age, sex, or race is a factor. The prevalence of anaphylaxis caused by penicillin and insect sting is not increased in pa-

tients with a personal or family history of atopy. However, once sensitized to a specific antigen, patients with positive skin tests for atopic reaction have a greater incidence of anaphylaxis than do nonatopic subjects. 1 A recent study reported that persons who have previously reacted to an antimicrobial drug have a ninefold increased risk of hypersensitivity reaction to another antibiotic. It is interesting that increased atopic manifestations (eg, severe cutaneous reactions, vasculitis) in response to certain drugs occur more frequently in patients with AIDS. 1 The reasons for these phenomena are unclear but may be related to altered host processing and immunologic responses to antigens caused by the coincident infection. 4 Mediators and mechanisms Mast cells and basophils produce diverse chemical mediators that

are readily released from stored granules on stimulation of the cell or are synthesized after activation and then released.s Important mediators are listed in table 2. The most common mechanism in anaphylaxis of clearly defined cause is the IgE-dependent immediate hypersensitivity reaction. Parenteral administration of antigen is the route most often implicated in severe anaphylaxis, but oral, topical, and inhalational administration has also been associated with anaphylactic reactions. Such reactions occur in persons who have become allergic to the inciting antigen as a result of prior exposure. Massive release of potent biochemical mediators from mast cells and basophils occurs on reexposure to the antigen owing to bridging of antigenspecific IgE molecules located on the cell surface. In addition to the known ability of mast cells and basophils to degranulate to IgE-mediated stimuli, these putative cells may be recruited into systemic reactions through other mechanisms independent oflgE. When combined with antigen, IgM and IgG antibodies can activate the complement system, which results in the release of complement fragments C3a and CSa into the surrounding fluid. These cleavage fragments are anaphylatoxins and

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Numerous agents (eg, opiates, curariform agents, highly charged antibiotics, drugs that create hyperosmolar conditions) have been implicated in anaphylaxis.

Table 1. Estimated incidence or prevalence of acute anaphylactic reactions Cause

Incidence or prevalence

General cause

1/2,700 hospitalized patients

Insect sting

0.4-0.8% of US population

Radiographic contrast material

1/1 ,000-14,000 procedures

Penicillin (fatal outcome)

1-7.5 per million treatments

General anesthesia

1/300 treatments

Hemodialysis

1/1,000-5,000 treatments

Immunotherapy (severe reaction)

0.1 per million injections

Adapted, with permission, from Metcalf DO. Acute anaphylaxis and urticaria in children and adults. In: Schocket AL, ed. Clinical management of urticaria and anaphylaxis. New York: Marcel Dekker, 1992:70-96.

Table 2. Mast cell and basophil mediators of anaphylaxis Primary (stored) mediators Histamine Chemotactic factors for neutrophils and eosinophils Proteoglycans (eg, heparin, chondroitin sulfate) Potent proteolytic enzymes (eg, trypsin, chymotrypsin)

Secondary (generated) mediators Prostaglandins Leukotrienes Platelet -activating factor Cytokines (interleukins and hematopoietic factors)

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may lead to anaphylaxis by stimulating release of mast cell and basophil mediators. 6 These mediators also directly affect smoothmuscle tone (which may influence vascular tone diffusely), vasopermeabiliry, and bronchial constriction. Numerous exogenous agents (eg, opiates, curariform agents, highly charged antibiotics, drugs that create hyperosmolar conditions) have been reported to be capable of causing direct degranulation of mast cells with histamine release. Idiosyncratic reactions to aspirin and structurally unrelated nonsteroidal antiinflammatory drugs are also occasionally implicated in anaphylactic events, the most common of which are bronchospasm and urticaria with angioedema. The tendency of these drugs to cause such reactions is associated with their ability to inhibit the arachidonic acid enzyme cydooxygenase, which preferentially diverts the arachidonate down the lipoxygenase pathway. The lipoxygenase products (ie, leukotrienes) mediate chemotaxis and are also potent stimulators ofbronchoconstriction and mucus secretion. 7 Other possible mechanisms of anaphylaxis include a wide array of endogenous cellular stimuli (eg, interleukins, hematopoi-

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When the respiratory and cardiovascular systems are involved in anaphylaxis, the risk of mortality becomes a significantly greater concern.

etic factors, histamine-releasing factors, neuropeptides, eosinophil major basic protein). However, the role of these factors has not been fully characterized.

Tommy C. Sim, MD Dr Sim is assistant professor of medicine and chief, allergy clinical service, division of allergy and immunology, department of internal medicine, University of Texas Medical Branch at Galveston.

Clinical features Signs and symptoms of anaphylaxis are similar, regardless of the cause. Characteristic clinical manifestations can appear in many organ systems; organ involvement differs from case to case. Signs and symptoms may range from mild to severe. Anaphylaxis usually begins within minutes of exposure to the causative factor, although onset may be delayed for several hours. Once under way, the reaction usually progresses in an explosive manner, reaching peak intensity within an hour. Nonfatal reactions usually resolve within 48 hours. After exposure to a triggering factor, patients may have early warning signs and symptoms, such as warmth, tingling, or pruritus, often affecting the scalp, external auditory meatus, lips, soles of the feet, or genital area. These initial symptoms rapidly evolve to include diffuse flushing, urticaria, angioedema, and nasal congestion. A feeling of impending doom may follow, with substernal pressure or constriction of

the throat with hoarseness, which heralds laryngeal edema. Hypotension leads to tachycardia, dizziness, and loss of consciousness, whereas bronchospasm causes wheezing and dyspnea. Cramping abdominal pain and hyperperistalsis may also result from visceral smooth muscle contraction. Nausea, vomiting, diarrhea, or tenesmus may occur. Hypotension may be compounded by covert thirdspace fluid in various visceral or-

gans. Because of uterine contractions, women who experience anaphylaxis may have pelvic pain or profuse, watery vaginal discharge, which may be bloodstained. This condition is usually self-limiting and lasts about 48 hours. Hemoconcentration and disorders of hemostasis have been observed. When the respiratory and cardiovascular systems are involved, the risk of mortality becomes a significantly greater con-

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Treatment of anaphylactic reactions is sequential, and parenteral epinephrine is the initial drug of choice.

cern. Respiratory failure may be the result of laryngeal edema or severe acute asthma. Cardiac arrhythmia, which may be supraventricular or ventricular in origin, may occur, probably secondary to myocardial ischemia or elevation of catecholamine levels. Peripheral vascular dysfunction, cardiac arrhythmias, or myocardial damage may result in cardiovascular collapse. fu a general rule, the severity of an anaphylactic reaction is direcdy proportional to the rapidity of onset. After treatment of an initial episode, 20% of patients have life-threatening recurrence of manifestations. 8 These "second wave" reactions can appear 8 to 12 hours after apparent remission of the reaction. Such "biphasic" anaphylaxis is distinct from persistent anaphylactic reactions, which may last from 5 to 32 hours despite aggressive therapy. The latter form of anaphylaxis occurs in up to 28% of patients. 9 Because of the possible recurrence of anaphylaxis, in-hospital monitoring of patients with severe acute reactions, particularly elderly patients with cardiovascular disease, is reasonable. Several nonimmunologic factors appear to increase the risk of anaphylaxis progressing to a severe or fatal outcome. Beta-

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adrenergic blocking agents seem to increase the likelihood and severity of anaphylactic reactions and interfere with the use of beta-adrenergic agonists to treat anaphylaxis. 10 An increase in the frequency and severity of angioedema resulting from therapy with angiotensin-converting enzyme inhibitors was recendy reported in patients with a history of idiopathic angioedema. 11 Moreover, in patients receiving hemodialysis, anaphylactic reactions were seen during treatment with angiotensin-converting enzyme inhibitors, and the reactions no longer occurred after the drugs were stopped. 12 Anaphylaxis seems to be twice as likely to be fatal in asthmatic patients as in nonasthmatics 13 and also is more likely to be severe or fatal in patients with congestive heart failure or arteriosclerotic coronary artery disease. In cardiac patients, poor cardiac compensatory mechanisms, ischemia, or elevated catecholamine level secondary to endogenous or exogenous causes is a plausible explanation for intensified reactions. Sequential treatment Anaphylaxis is a medical emergency requiring prompt and appropriate treatment (table 3). Although anaphylactic reactions are

not especially common, it is imperative that every physician be aware of correct treatment, because failure to treat adequately can be fatal. Favorable outcome of treatment is dependent on the rapid institution of appropriate volume repletion and pharmacologic agents. Treatment of anaphylactic reactions is sequential. Parenteral epinephrine is the initial drug of choice. If the site of antigen exposure is evident, steps should be taken to reduce the rate of absorption of antigen from that site. For example, in a patient stung on the arm by a bee, the stinger should be scraped off with a knife or fingernail to remove the venom sac and a tourniquet should be applied to the arm. Epinephrine can be injected into the site of antigen exposure as well, to induce vasoconstriction. However, if parenteral epinephrine is used in conjunction with a tourniquet, subsequent injections should be made in a nonocduded limb. The drug is rapidly metabolized. Therefore, epinephrine can be given intermittendy every 15 to 20 minutes, depending on the severity of the anaphylaxis, or by continuous intravenous infusion to maintain adequate blood pressure. Further treatment of anaphy-

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The use of corticosteroids may be justified to prevent complications of late anaphylactic reactions resulting from delayed antigen absorption.

laxis requires attention to both adequate oxygenation and reversal of hypotension. In patients with respiratory insufficiency, oxygenation by controlled flow in conjunction with administration of a beta agonist is essential. Endotracheal intubation or emergency tracheostomy should be considered if adequate oxygenation cannot be maintained because of increasing airway obstruction from bronchospasm or laryngeal edema. A major portion of the vascular collapse that occurs during acute anaphylaxis is due to leakage of fluids from the intravascular to the extravascular space and to pooling of blood in the large-capacity venous splanchnic bed. Hypotension requires fluid replacement, including administration of plasma-expander agents and possibly an alpha-adrenergic agent, dopamine hydrochloride (Dopastat, lntropin), or both. The volume of fluids that must be replaced can be great. When hypotension persists or congestive heart failure is suspected, measurement of central venous pressure or pulmonary artery wedge pressure may help guide the amount of fluid replacement. Late reactions resulting from delayed antigen absorption or

biphasic allergic reactions are being recognized with increasing frequency. Such reactions may justify the use of corticosteroids to avert late complications. Other pharmacologic agents, often considered secondary drugs, may be useful, especially in patients whose response to epinephrine is sluggish or in whom biphasic or recurrent anaphylactic reactions are likely to develop. Such secondary drugs include aminophylline (Phyllocontin) and antihistamines (both histamine 1 and histamine2 blockers). In addition to providing bronchodilation, aminophylline has been shown to stimulate respiratory drive, augment cardiac contractions, and promote diaphragmatic contractility. Although the issue is debatable, antihistamines may also be useful in treatment of anaphylaxis. Potentially deleterious cardiovascular effects of histamine release include hypotension, coronary vasoconstriction, increased myocardial oxygen demand, and dysrhythmia. Antihistamines can also be used to decrease the discomfort often associated with concomitant skin reactions (eg, urticaria, angioedema). However, these are ancillary agents and their use is not a substitute for epinephrine and fluids.

The increased use of beta blockers in recent years has complicated treatment of anaphylaxis, because beta blockers seem to potentiate the reaction, possibly by reducing the response to infused beta agonists in both the cardiovascular and pulmonary systems.14 This condition may cause persistent bronchospasm and protracted hypotension leading to bradycardia. Patients taking a beta blocker may require more than the usual amounts of epinephrine or beta-agonist therapy. Use of a topical beta blocker for treatment of glaucoma may be an underlying cause of unexplained, protracted anaphylaxis. Other pharmacologic agents to be considered include intravenous isoproterenol hydrochloride (lsuprel), atropine sulfate, and glucagon. Transvenous pacing may have an effect. 15 Stress-induced release of endogenous opioids (ie, endorphins) may be a significant factor in the pathogenesis of shock by contributing to hypotension and cardiodepression. Naloxone hydrochloride (Narcan), an opiate antagonist, has been successfully used in experimental and clinical shock caused by diverse factors. 16 Although these results are of interest, naloxone should be used with caution pending results of

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Use of a topical beta blocker for treatment of glaucoma may be an underlying cause of unexplained, protracted anaphylaxis.

carefully controlled clinical trials. Complications from either the anaphylactic episode itself or from its treatment may be severe (table 4). Thus, treatment should be individualized on the basis of any underlying medical conditions and the severity of the episode. Causative factors In some patients, the cause of an anaphylactic reaction is apparent from the events immediately preceding the episode. However, a significant number of patients have recurrent episodes for which no cause can be found or which have an unusual cause that may not be immediately apparent. Table 5 lists some of the many substances that are known to cause or have been associated with anaphylactic reactions. Some causes of anaphylaxis have long been recognized. Other causes have been reported only recently, including exercise, intake of food preservatives or angiotensin-converting enzyme inhibitors, latex hypersensitivity, exposure to human seminal fluid, and hormonal changes during menses. 1c 2" Exercise-induced anaphylaxis is a unique clinical syndrome first described in 1980. A puzzling aspect is that it does not always occur after exercise, which

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Table 3. Management of systemic anaphylaxis Initial therapy 1. Stabilize the airway. If symptoms of upper airway obstruction develop, endotracheal intubation, puncture of the cricothyroid membrane, or emergency tracheostomy may be required. 2. Inject epinephrine, 0.3-0.5 ml of aqueous 1:1,000 solution, subcutaneously. Dose may be repeated q15-20min if needed. 3. Obtain venous access (with 18-gauge or larger catheter, if possible) for volume replacement and IV administration of medication. 4. If applicable, place tourniquet above site of injection, sting, or contact to reduce systemic absorption of the agent. Loosen q5min to maintain adequate peripheral circulation. Epinephrine may be injected into the site to induce vasoconstriction. 5. Record vital signs often (initially, at least q15min). If symptoms of severe reaction are present, admit patient to a hospital and monitor. Hypotension 1. Place patient in Trendelenburg 's position. 2. Administer rapid fluid replacement with either saline or colloidal solution (up to 1 L q20-30min may be required). 3. For persistent or recurrent symptoms, administer IV epinephrine (0.3-0.5 ml of aqueous 1:10,000 solution) slowly into a nonoccluded extremity or start a continuous infusion (0.025-0.1 J..Lg/kg per min). Weigh risks against possible benefits. 4. For hypotension not responding to the measures described, continuous infusion of norepinephrine (Levophed) (0.05-0.5 J..Lg/min), dopamine HCI (Dopastat, lntropin) (2-1 0 J..Lg/kg per min), or both may be needed, titrated to maintain preanaphylaxis systolic blood pressure. 5. Severely ill or fragile patients may benefit from measurement of central venous pressure or pulmonary arterial and capillary wedge pressures with a flow-directed pulmonary catheter. 6. For cardiac patients who have received beta blockers, IV administration of glucagon (5-15 J..Lg/min), atropine sulfate (0.3- to 0.5-mg doses repeated q5-1 Omin as needed or until a total dose of 2 mg is reached), and isoproterenol HCI (lsuprel) (~2 J..Lg/min) may be necessary. 7. For shock, naloxone HCI (Narcan), O.Q1 mg/kg up to a 0.4-mg dose, may be tried with caution. 8. Military antishock trousers may be effective in increasing central volume. 9. Use antiarrhythmic agents as needed.

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A few patients may experience lgE-mediated anaphylaxis intraoperatively from allergens leached from latex rubber gloves worn by surgeons.

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Table 3. Continued Bronchospasm and need for enhanced oxygenation 1. Administer oxygen by nasal catheter or face mask. 2. For mild bronchospasm: Administer a nebulized beta-adrenergic agonist (eg, albuterol [Proventil, Ventolin], 0.5 ml of the 0.5% solution in 2.5 ml saline, or metaproterenol sulfate [Aiupent, Metaprel], 0.3 ml of the 0.5% solution in 2.5 ml saline, q15-30min as needed). For severe bronchospasm: Also administer aminophylline (Phyllocontin), loading dose of 6 mg/kg IV over 30-min period (if patient has not been taking theophylline regularly), followed by 0.3-0.9 mg/kg per hr as maintenance dose. If necessary, terbutaline sulfate (Brethine, Bricanyl), 0.25 mg, may be injected subcutaneously and a second dose given in 15-30 min (total dose not to exceed 0.5 mg in 4-hr period). 3. IV corticosteroid therapy (eg, methylprednisolone [Medrol], 1 to 2 mg/kg or maximum of 250 mg q4-6h) may be helpful if significant symptoms persist after 1-2 hr of vigorous therapy. Urticaria and angioedema 1. Administer a histamine 1 (H 1) blocker (eg, diphenhydramine HCI [Benadryl, Diphenacen-50], hydroxyzine [Atarax, Vistaril], 25-50 mg IM or PO q6-8h as needed). Nonsedating H 1 antihistamines (eg, terfenadine [Seldane], 60 mg PO q12h) are also effective. 2. Although not proven to be of benefit in this situation or in hypotension resulting from histamine2 (H 2) receptor-induced vasodilatation, H2 blockers (eg, ranitidine [Zantac], cimetidine [Tagamet], 300 mg IV or PO q6-8h) may be added. Be cautious of possible drug interaction with theophylline (especially with cimetidine). Miscellaneous • If prolonged treatment has been required, send blood sample for hemogram and electrolyte evaluation and, if indicated, order studies for arterial blood gases and theophylline and drug levels. • Order chest x-ray films in cases of poorly responsive bronchospasm or localized abnormality on examination. • Order electrocardiogram to monitor for possible myocardial ischemia or arrhythmias. • Consider use of corticosteroids to prevent the late recurrence of anaphylactic symptoms.

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makes exercise challenge testing difficult. In some patients, exercise must occur postprandially or after ingestion of a specific food (eg, shrimp, wheat, celery) to produce the full-blown syndrome. 21 Recently, patients with spina bifida have been reported 22 to experience anaphylactic reactions to plastic polymers and plasticizers that make up the retention tips in enema kits. These patients also have an increased incidence of sensitization to rubber and may experience IgE-mediated anaphylaxis intraoperatively from allergens leached from latex rubber gloves worn by surgeons. 23 Reactions have also been produced by the latex-cuffed rectal catheters used to administer barium enemas. Some cases of intraoperative anaphylaxis attributed to drug allergy may actually have been caused by latex hypersensitivity.

Differential diagnosis Several reactions may be mistaken for anaphylaxis (table 6) and must be excluded during diagnosis. Certain clinical features of anaphylaxis are also seen with conditions causing sudden loss of consciousness (eg, vasovagal syncope, seizures, stroke, myocardial infarction, arrhythmia) or acute respiratory decompensation (eg, status asthmaticus, epiglottitis, continued

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Some disorders with cutaneous or respiratory manifestations (eg, mastocytosis, Chinese restaurant syndrome) may mimic anaphylaxis.

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Table 4. Possible complications of anaphylaxis and its treatment

Of anaphylaxis Persistent hypoperfusion leading to myocardial infarction, cerebral ischemia, and renal failure Respiratory failure with or without upper airway compromise Death

Of treatment Of epinephrine, norepinephrine (Levophed), or dopamine HCI (Dopastat, lntropin) therapy Hypertension (leading to myocardial ischemia or cerebrovascular accident) Cardiac arrhythmias Tissue necrosis (extravasation into extravascular tissues) Of vigorous intravenous fluid administration Congestive heart failure Pulmonary edema Electrolyte imbalance Of aminophylline (Phyllocontin) therapy Gastrointestinal distress Cardiac arrhythmias Seizures Of beta-adrenergic agonist therapy Tremor, nervousness Cardiac arrhythmias Of antihistamine therapy Sedation Anticholinergic effects (eg, acute urinary retention, blurred vision)

airway obstruction from foreignbody aspiration, pulmonary embolism). Some disorders with cutaneous or respiratory manifestations may mimic anaphylaxis (eg, mastocytosis, carcinoid syndrome, Chinese restaurant syndrome, scombroid toxin-induced reactions, adverse pharmacologic reactions to drugs). Factitious anaphylaxis (eg, panic attacks) and malingering are unusual and may require psychological evaluation. Recurrent anaphylaxis without an apparent, common cause must be investigated appropriately. For example, angioedema may be due to hereditary angioedema, in which the C 1 esterase inhibitor is low (type 1) or dysfunctional (type 2). 24 Nonfamilial forms of C 1 esterase inhibitor deficiency have been described with lymphoproliferative and connective tissue disorders. Preventive measures Death from anaphylaxis is avoidable if correct treatment is instituted quickly. Unfortunately, the necessary treatment and expertise are not always available. Therefore, avoiding anaphylaxis is of paramount importance and constitutes the safest and most reliable therapy. Table 7 describes measures to consider in prophylactic management of anaphylaxis.

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Patients who experience exercise-induced anaphylaxis should not exercise alone.

Susceptible persons should take steps to limit their exposure to agents known to precipitate anaphylaxis. Patients who have an anaphylactic reaction to Hymenoptera stings should modifY their habits to minimize the chances for exposure, and specific immunotherapy is warranted." 5 Persons manifesting true anaphylaxis to foods or food additives should vigilantly avoid unwitting ingestion, particularly when eating away from home. 26 Patients who experience exercise-induced anaphylaxis need to modifY their exercise regimens to decrease the likelihood of inducing symptoms.17 They should not exercise alone, after eating, or after taking a nonsteroidal anti-inflammatory drug. Asthma therapy should be optimized before high-risk procedures are undertaken. Beta blockers, angiotensin-converting enzyme inhibitors, and nonsteroidal anti-inflammatory drugs, including aspirin, should be discontinued during high-risk situations. In some instances, administration of agents known to cause anaphylaxis is medically necessary in persons at high risk. In such situations, acute desensitization may minimize the likelihood of anaphylactic reactions. Management guidelines usually include pharmacologic pretreatment of sus-

Table 5. Causes of and factors associated with anaphylactic reactions lgE-mediated reactions Antibiotics and other drugs Food Foreign proteins (eg, horse serum, vaccines, chymopapain) Hymenoptera stings Immunotherapy Latex and other rubber-derived products Seminal plasma

Complement-mediated reactions Dialysis membranes Human plasma and blood products

Direct activation of mast-cell mediator release Aminoglycosides Muscle-depolarizing drugs Opiates Radiocontrast material Vancomycin (Vancocin, Vancoled)

Modulation of arachidonic acid metabolism Aspirin and nonsteroidal anti-inflammatory drugs

Idiopathic, recurrent anaphylaxis Factors associated with initiation of anaphylaxis Exercise Hormonally related reactions Urticaria (with anaphylaxis) induced by physical agent Sulfite sensitivity

ceptible persons in an attempt to block or modifY reactions. 27 Oral administration of any drug whenever possible and observation for 30 minutes or more after the first dose of a drug that is commonly associated with ana-

phylaxis also decrease risk. Evaluation and counseling of patients with anaphylaxis of unknown cause may be particularly challenging. The most valuable tool is a history, taken carefully with repeated probing for subtle

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Patients in whom a cause for anaphylactic reactions cannot be fully identified or avoided should wear some form of medical identification and carry a self-administered epinephrine device.

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Table 6. Differential diagnosis of anaphylaxis

Table 7. Prophylactic management of anaphylaxis Provide complete education about avoidance

Acute respiratory decompensation (eg, airway obstruction)

Administer desensitization therapy as appropriate (eg, against penicillin, aspirin, Hymenoptera and fire ant venom)

Carcinoid syndrome Chinese restaurant syndrome (ie, reaction to monosodium glutamate) Drug reaction (direct side effects)

Ensure proper identification of triggers (eg, with medical identification bracelet) Teach use of self-administered epinephrine HCI (eg, with Epi-Pen, Ana-Kit) Consider pharmacologic prophylaxis (eg, prednisone, histamine, and histamine 2 blockers, and/or cromolyn sodium [lntal])

Factitious anaphylaxis (eg, panic attack) Hereditary angioedema Malingering Primary medical disorder (eg, seizure disorder, stroke, hypoglycemia, myocardial infarction, dehydration, sepsis) Scombroid toxin-induced reaction Serum sickness Systemic mastocytosis Vasovagal collapse

exposure to possible causes. Treatment programs for patients with recurrent idiopathic anaphylaxis are individualized. Patients with regular attacks of idiopathic anaphylaxis or with sensitivity to factors that make repeated episodes

possible often benefit from daily doses of antihistamines and/or cromolyn sodium (Imal), sometimes with the addition of alternate-day steroid therapy. 28 When a cause cannot be further identified or avoided, as in the case of insect stings, specific food ingestion, or unexplained recurrent anaphylaxis, patients should wear some form of medical identification tag containing the relevant information and should carry a self-administered epinephrine device (eg, EpiPen, Ana-Kit). These patients should be instructed in the use of the device and told to also take an amihistamine and an oral steroid, if available, and proceed to the nearest hospital emergency de-

partment for medical assistance if they have an anaphylactic reaction. Radiocontrast material, commonly used in diagnostic radiology, is usually hyperosmolar. The hypertonicity of this material causes many significant undesirable side effects, including anaphylactic reactions. 29 Generalized urticaria, bronchospasm, hypotension, or a combination of the three may occur in as many as 10% of patients undergoing procedures using this material. 29 Atopy to shellfish or iodides does not predispose a person to anaphylactic reactions to radiocontrast material. Recurrence rates have been reported to range from 25% to 46% in persons who

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3. Administer a histamine2 antagonist (eg, ranitidine [Zantac] or cimetidine [Tagamet], 300 mg PO) 3 hr before administration of radiocontrast material.

myelography, and retrograde pyelography. Therefore, patients with a history of reaction who are to undergo one of these procedures should be premedicated. Occasionally, a high-risk patient must undergo an emergency radiographic procedure and there is no time to use a pretreatment regimen. For these cases, an emergency protocol has been proposed (table 8). 1"

4. Administer ephedrine, 25 mg PO, 1 hr before administration of radiocontrast material (withhold if patient has hypertension, coronary artery disease, or arrhythmia).

Summary

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Table 8. Pretreatment protocol for sensitivity to radiocontrast material* 1. Administer prednisone (50 mg PO) 13, 7, and 1 hr before administration of radiocontrast material. 2. Administer diphenhydramine HCI (Benadryl, Diphenacen-50), 50 mg IM or PO, or terfenadine (Seldane), 60 mg, 1 hr before administration of radiocontrast material.

5. Emergency protocol: Administer hydrocortisone sodium succinate (A-Hydrocort, Solu-Cortef), 200 mg IV, or methylprednisolone (Medrol), 200-250 mg IV, immediately and q4h until radiographic procedure is complete, plus diphenhydramine, 50 mg IM, 1 hr before the procedure. *Dosages given are for adults.

have had a reaction to radiocontrast material. 29 The risk of another reaction on reexposure cannot be predicted by pretesting. If a study using radiocontrast material must be performed in a person known to be sensitive to such dye, a pretreatment regimen (table 8) should be followed. In patients with a history of asthma, theophylline should be added to the pretreatment regimen. Use of the newer low-osmolarity radiocontrast material is advisable in persons with a history of adverse

reaction to conventional radiocontrast material. Even with use of these precautions, anaphylactic reactions to radiocontrast material can still occur. Therefore, documenting reasons why the study must be performed and explaining the potential risks to the patient are imperative. It is important to remember that reactions can also occur when radiocontrast material is administered by nonvascular routes. Reactions have occurred during hysterosalpingography,

Anaphylaxis is a dramatic, major medical emergency. Understanding of the pathogenesis, emergency treatment, and subsequent prophylaxis can reduce both morbidity and mortality. Treatment of anaphylaxis should begin with a high degree of suspicion. Taking a wait-and-see attitude in hopes that the reaction will be mild may have serious results. RJVI Earn credit on this article. ~ See CME Quiz.

Address for correspondence: Tommy C. Sim, MD, Division of Allergy and Immunology, Department of Internal Medicine, Rt G-62, University of Texas Medical Branch at Galveston, Galveston, TX 77555-1031.

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NAPROSYN' (NAPROXEN) 500 mg tablets

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:~~P!· h~oa~~~a~~~Y~~~f~~~~~~~~~~~~~~a~Xtt~~~r ~~~ ~~:~e~~. nasal polyps, urt1cana. and hypotenSion assoc1ated w1th NSAIDs before startmg therapy If such symptoms occur. d1scont1nue the drug. W111l1p: Senous Gl tox1city such as bleedmg, ulceration.

:n~~;~:.a~~~~i~n~~~~:~da~hr~:a~~~~~~th ::~~ust R~~~~~ aYert for ulceratton and bleeding m such pattents even m the absence of prevtous Gl tract symptoms. In cltmcal tnals, symptomattc upper Gl ulcers. gross bleedmg or perforation appear to

~~utJo~t a~?:~:~~a~le~~~ 0t r~::~n~~~ r~~~~!~~. t·n~o~~"1~~·,e n"t~ ~reoP~t ~~~a~~~~s ~~~~~;~~~:~~;sa~;;:~~~; ~~~~~i~,~~~~~;~u~~:! ~~g:~~e~b~ "aot:rt~:s~,~~:~ve~VP~~,g~f'~t u~~~~~~o~n~"~P~:~;~s~ 1

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factors known to be assoctated with pepttc ulcer dtsease. such as

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~ceonh~~:;1 a~~0~,~~·inei~ea: ~;~~- ft~~~r~~ J~·9eb,j~~te~e;!~~~~~~

seem to tolerate ulceration or bleeding less well than others and most spontaneous reports of fatal Gl events are m th1s population In considering the use of relatively large doses (w1thm the recommended dosage ran~e). suff1c1ent benefit should be ant1c1pated to offset the potential 1ncreased risk of Gl tox1c1ty. Pree~utlonl: 00 NOT GIVE NAPROSYN• (NAPROXEN~ CONCOMITANTLY WITH ANAPROX• (NAPROXEN SODIUM DR ANAPROX• OS (NAPRDXEN SODIUM) SINCE THEY B0 H CIRCULATE IN PLASMA AS THE NAPROXEN ANION. Acute Interstitial nephritis w1th hematuna. proteinuria, and nephrotic syndrome has been reported Patients with 1mpa1red renal tunct1on. heart failure. liver dysfunction, patients taking diuretiCS, and the elderly are at greater nsk of overt renal decompensation. It this occurs. d1scontmue the drug. Use w1th caut1on and mon1tor serum creatimne and/or creatinine clearance in patients with s1gmfica_ntly 1mp~1red renal function Use caut1on m pat1ents w1th baselme creatmme clearance less 1

~~a~~~n~L~~~~~~t~ro~~ ~~io~:s1,!~re~~Zia~~~r i~~~~~o~~~r~,?~

NSAIOs, borderline elevat1ons of liver tests may occur 10 up to

i(a~SI~fnf~:~~t~o~~~~Ja~t,~~e~fev~i~~~n o1ng~a~r~; gG8f occurred

10

controlled chmcal tnals in less than 1% of pat1ents

~=r~~~~e1~r~~c~~~~fY. 1~):~~;n~~aaus~d~~~e~g~s ~~~ailf ~~~f~~~~~ 1

mamfestations occur (e.g.,

eosmophll~a

or rash), d1scontmue ther-

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mg adr~nal insufficie_ncy and exa~erbat10n of arthritis symptoms. Oetermme hemoglobin values penod1cally for pat1ents with 101t1al values of 10 grams or less who rece1ve long-term therapy. Penpheral edema has been reported. Therefore. use w1th caut1on 10 patients w_ith fl~id retent1on_, hypertension or heart failure. The

:e~\ri~'/~t:~at~~n.a~!~~~~~n~a:~~rr ~f~~v~~:~,c ~~lu;e~uocneduct ophthalmic studies if any change or disturbance 1n VISIOn occurs. For patients with restricted sodium Intake. note that the 1

~:~:~o~d;~~~~sot NSA~b~~a~ c:~s~ ~~Co~~g~t~~~~~ar~f; 8

1

there are more senous s1de effects, such as Gl bleeding, which may re~ult in hospitalization a~d even fatal outcom_es. Physic1ans may w1sh to discuss with pat1ents the potentiai nsks and likely

~~e~~,g~sN~:~~itti~;~r:,~tr/t~~f~:~r ;il,"~ui~%\1~s u~ea~ fg: an acceptable alternative. Patients should use caut1on for actiVIties requiring alertness 1f they expenence drowsmess, diumess, vertigo or depression dunng therapy. llllarllory Tests: Because senous Gl tract ulceration and bleedmg can occur Without warn~~~~{~~0~5fh~~m:n~h~~~~~~~h~~t;r t~:tl~~~/~;n~~g~~ f~i~

follow-up. Drug llterKtloa: Use caut1on when 8ivmg concomi1

~~I~e w~~h s~~fo~~j~~~~:pe,uar~~~~i~~ ;a~~fh,~~r g~:~~~·los~~~~~.-

probenecid; or methotrexate. o.. g/llllarltory Testl•ter~ctiOM: The drug may decrease platelet aggregation and prolong bleedmg tmle or mcrease urinary values for 17-ketogenlc steroids. Temporarily stop therapy for 72 hours before domg adrenal function 5 1

~~:':i~~:uX ~i'~~t~;:e~~u~~t~h~~;~~?n~s::i~~~~e ~f ~rc~~:

genicity. Pr1181ocy: Category B. Do not use dunng

pr~nancy

:~~l:eai%i~e~edinA~~~~i~~ ~~f~~~,'·~~\:'l~:n~: ~?nt;1:

~";k~,~~~ ~~ ~~~k?n ~~~~dr~~a~v~~il~ ~~~s ng; ;~;e=~

Ructloa: In a study, Gl react1ons were more frequent and severe 1n rheumatoid arthritis patients on 1,500 mg/day than 1n those on 750 mg/day. In studies 1n children w1th 1uvemle arthntiS. rash and prolonged bleeding times were more frequent, Gl and CNS reac-

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Gl: The most frequent complaints related to the Gl tract constipah_eartburn,• abdominal pain,· nausea~ dyspeps~a. diarrhea, stomatitis. CNS: headache: dizziness: drowsiness: light-headedness. vertigo. Oermatolog1c: Itching (pruritus): skin eruptiOns:

tion~

r;~hli~~~c~~~~~~a~P~;ft~~ba~~-iab~~~~~~~~~~t:u~~e~e::-

dyspnea: palpitations. General: thirst Incidence Less Than 1%. PTobable causal Relationship: Gl: abnormal liver function tests,

::~~a. ~:r~~:~~ra~~dri~itr~r~~~~ogn3n~~~a~~~~~~io~.u~~i~~

1n~ .. Renal: g~merular nephntis, hematuria, _hyperkalemia, i_nterstltlal nephntiS, nephrotic syndrome, renal disease, renal failure, re~~l papillary necrosis. Hematologic: agranulocytOSIS, eosinophilia, granulocytopema. le~kop~nla . ~hrombocytopen1a CNS· depressiOn, dream abnormalities, 1nab!l1t)' :o concentrate. 1nsom-

~~·. ~~~;~e~~i~~: ;~~m~~~i~f~~ ~nknr~~~e~~rS~!~~~i~e~~~:.-

hearmg impairment. CardiOvascular: congest1ve heart fa1lure Respiratory· eosmophil1c pneumonitis. General: anaphylactoid reactions. menstrual disorders. pyrexia (chills and lever). Causal

:e~~~~~:u;~":n~n~~~~~~~~c~n~f~s~~~~~:gn_h&";~~-

log_l~: ep1der~al necrolysis, erythema mult1forme, photosensit_IVIty rea~t1ons resembling porphyria cutanea tard~ and epidermolysrs bullosa, Stevens-Johnson syndrome. urticana. Gl non-peptiC Gl ulceration, ulcerative stomatitis. cardiovascular vasculitis. General: angioneurotic edema, hyperglycemia, hypo-

H~.~.~~ ~are:a;:t~~~~~~:Sh:dea~~~~~~-'"~:~

stomach and use usual supportive measures. In ammals 0.5 g/kg ol actMited charcoal reduced plasma levels ol naproxen. Clutlal: ~~~'ror\~i~~~:~~o~~:~ prescnption See pack-

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' Incidence of reported reaction 3%-9%. Where unmarked, incidence less than 3%. L.=-L.- - - - - " · U.S. patent nos. 3,904,682. 3,998.966 and others. © 1991 Syntex Puerto Rico, Inc Rev. 39 September 1990

References I. Settipane GA, Klein DE, Boyd GK. Relationship of atopy and anaphylactic sensitization: a bee sting allergy model. Clin Allergy 1978; 8(3):259-65 2. Moseley EK, Sullivan 1). Allergic reactions to antimicrobial drugs in patients with a history of prior drug allergy. (Absrr) J Allergy Clin Immunol1991;87(1 Pt 2):226 3. Carr A, Cooper DA, Penny R. Allergic manifestations of human immunodeficiency virus (HIV) infection. J Clin lmmunol 1991; II (2):55-64 4. Sim TC, Alam R, Engler DB, eta!. Skin reactivity to intradermal codeine and histamine in AIDS patients as compared to normal and allergic subjects. (Abstr) J Allergy Clin lmmunol 1991 ;87(1 Pt 2): 159 5. DeJamatt AC, Grant JA. Basic mechanisms of anaphylaxis and anaphylactoid reactions. lmmunol Allergy Clin North Am 1992;Aug 6. Dvorak AM, Lett-Brown M, Thueson D, eta!. Complement-induced degranulation of human basophils. J lmmunol1981;126(2):523-8 7. Manning ME, Stevenson DD. Pseudoallergic drug reactions: aspirin, nonsteroidal antiinflammatory drugs, dyes, additives, and preservatives. Immunol Allergy Clin North Am 1991; II (3):659-78 8. Stark BJ, Sullivan 1). Biphasic and protracted anaphylaxis. J Allergy Clin lmmunol 1986;78(1 Pt 1):76-83 9. Sheffer AL. Anaphylaxis_ Insights in Allergy 1990;5(3): 1-8 10. Toogood JH. Risk of anaphylaxis in patients receiving beta-blocker drugs. J Allergy Clin lmmunol1988;81(1):1-5 11. Orf.m N, Patterson R, Dykewicz MS. Severe angioedema related to ACE inhibitors in patients with a history of idiopathic angioedema. JAMA 1990;264(1 0): 1287-9 12. Verresen L, Waer M, Vanrenterghem Y, eta!. Angiorensin-converting-enzy•nt inhibitor; and anap 1 :1lactoid reactions to high-flux membrar:e dix sis. Lancet 1990;336(8727): 1360-2 13. DM, Alpern MB, VJSintainer PF, eta!. !ncr, tsed risk for anaphylactoid reaction fram wntrast media in patients on betaadrenergic ''lockers or with asthma. Ann Intern Med !991;115(4):270-6 14. Jacobs RL, Rake GW Jr, Fournier DC, eta!. Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade_ J Aller-

Lang

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gy Clin lmmunol1981;68(2):125-7 15. Bochner BS, Lichtenstein IM. Anaphylaxis. N EnglJ Med 1991;324(25):1785-90 16. Gullo A, Romano E. Naloxone and anaphylactic shock. (Letter) Lancet 1983; I (8328): 819 17. Sheffer AL, Austen KF. Exercise-induced anaphylaxis. J Allergy Clin lmmunol1984;73(5 Pt 2):699-703 18. Slater JE. Rubber anaphylaxis. N Eng! J Med 1989;320(17):1126-30 19. Bernstein IL, Englander BE, Gallagher JS, eta!. Localized and systemic hypersensitivity reactions to human seminal fluid_ Ann Intern Med 1981;94(4 Pt 1):459-65 20. Burstein M, Rubinow A, Shalit M. Cyclic anaphylaxis associated with menstruation. Ann Allergy 1991;66(1):36-8 21. Novey HS, Fairshter RD, Salness K, eta!. Postprandial exercise-induced anaphylaxis. J Allergy Clin lmmunol 1983;71 (5):498-504 22. Lozynsky OA, Dupuis L, Shandling B, et a!. Anaphylactoid and systemic reactions following saline enema administration: six case reports. Ann Allergy 1986;56(1):62-6 23. Shapiro GG, Vtrant FS, Bums Mw, eta!. Intraoperative cardiovascular collapse due to latex allergy. (Abstr) J Allergy Clin lmmunol 1991;87(1 Pt 2):270 24. Sim TC, GrantJA. Hereditary angioedema: its diagnostic and management perspectives. Am J Med 1990;88(6):656-64 25. Reisman RE. Stinging insect allergy: progress and problems. (Editorial) J Allergy Clin lmmunol 1985;75(5):553-5 26. Sachs MI, Yunginger jw. Food-induced anaphylaxis. lmmunol Allergy Clin North Am 1991; II (4):743-56 27. Patterson R. Diagnosis and treatment of drug allergy_ J Allergy Clin lmmunol 1988; 81 (2):380-4 28. Wiggins CA, Dykewicz MS, Patterson R. Idiopathic anaphylaxis: a review. Ann Allergy I 989;62(1): 1-4 29. Erffineyer JE, Siegle RL, Lieberman P. Allergy grand rounds: anaphylactoid reactions to radiocontrast material. J Allergy Clin lmmunol1985;75(3):401-IO 30. Greenberger PA, HalwigJM, Patterson R, et a!. Emergency administration of radiocontrast media in high-risk patients_ J Allergy Clin lmmunol 1986;77(4):630-4

ANAPHYLAXIS • VOL 92/NO 5/0CTOBER 1992/POSTGRADUATE MEDICINE

Anaphylaxis. How to manage and prevent this medical emergency.

Anaphylaxis is a dramatic, major medical emergency. Understanding of the pathogenesis, emergency treatment, and subsequent prophylaxis can reduce both...
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