What is the standard emergency treatment for anaphylaxis

Approach Considerations

Anaphylaxis is a medical emergency that requires immediate recognition and intervention. Basic equipment and medication should be readily available in the physician’s office. Lieberman et al have described this in great detail. [26, 47, 67, 68, 69]

Prehospital patients with symptoms of severe anaphylaxis should first receive standard interventions. Interventions include high-flow oxygen, cardiac monitoring, and intravenous (IV) access. These measures are appropriate for an asymptomatic patient who has a history of serious reaction and has been re-exposed to the inciting agent. Measures beyond basic life support (BLS) are not necessary for patients with purely local reactions.

Disposition of patients with anaphylaxis depends on the severity of the initial reaction and the response to treatment. Patients with non–life-threatening symptoms may be observed for 4-6 hours after successful treatment and then discharged. Patients who have refractory or very severe anaphylaxis (with cardiovascular and/or severe respiratory symptoms) should be admitted or treated and observed for a longer period in the emergency department (ED) or an observation area.

Diagnosis and management guidelines are available from the American Academy of Allergy, Asthma, and Immunology; the American College of Allergy, Asthma, and Immunology; and the Joint Council of Allergy, Asthma, and Immunology. [47]

Go to Pediatric Anaphylaxis and Pediatric Exercise-Induced Anaphylaxis for complete information on these topics.

Initial Emergency Department Interventions

The 2010 Joint Task Force anaphylaxis parameter update, the 2011 World Allergy Organization anaphylaxis guidelines, [48] the 2010 NIAID-sponsored expert panel report [66] , and the 2014 practice parameters from the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Council of Allergy Asthma and Immunology [70, 71] have similar recommendations for immediate treatment in the ED. It should begin with monitoring and treatment, including oxygen, cardiac monitoring, breathing, mental status, skin, and a large-bore IV with isotonic crystalloid solution. At the same time, where appropriate, the ED team should call for specialized help, particularly a resuscitation team. Further intervention depends on severity of reaction and affected organ system(s), but the guidelines recommend the injection of epinephrine and placing the patient in a supine position (or position of comfort if dyspneic or vomiting) with the legs elevated.

Airway management

For the initial assessment, check the airway closely. If needed, establish and maintain an airway and/or provide ventilatory assistance. Assess the level of consciousness and obtain blood pressure, pulse, and oximetry values. Place the patient in the supine position with legs elevated, and begin supplemental oxygen.

Establishing and maintaining an airway or providing ventilatory assistance may be necessary. One of the quickest, easiest, and most effective ways to support ventilation involves a 1-way valve facemask with oxygen inlet port (eg, Pocket-Mask [Laerdal Medical Corporation, Gatesville, Tex] or similar device). Artificial ventilation via the mouth-to-mask technique with oxygen attached to the inlet port has provided oxygen saturations comparable to endotracheal intubation. Patients with adequate spontaneous respirations may breathe through the mask.

Standard rapid sequence induction (RSI) techniques can be used but may cause loss of the airway in a patient whose airway anatomy is altered by edema. Severe laryngeal edema may occur so rapidly during anaphylaxis that endotracheal intubation becomes impossible. Epinephrine may rapidly reverse airway compromise. If the edema does not reverse promptly with epinephrine, an endotracheal tube should be inserted promptly. Alternatively, it may be preferable to defer intubation and instead ventilate with a bag/valve/mask apparatus in the interim.

In extreme circumstances, cricothyrotomy or catheter jet ventilation may be lifesaving when orotracheal intubation or bag/valve/mask ventilation is not effective. Cricothyrotomy probably should be attempted rather than an emergency tracheostomy because it is easier to perform.

Wheezing or stridor indicates bronchospasm or mucosal edema. Treatment with epinephrine and inhaled beta-agonists is effective for these indications. Inhaled beta-agonists are used to counteract bronchospasm and should be administered to patients who are wheezing.

Recommendations to treat refractory bronchospasm with corticosteroids have been made because of their effectiveness in reactive airway disease. As in asthma therapy, onset of action is delayed for several hours. Aminophylline also has been recommended for bronchospasm in anaphylaxis and may be more rapidly effective than corticosteroids.

For bradykinin-mediated angioedema (including angioedema due to angiotensin-converting enzyme [ACE] inhibitors), antihistamines and corticosteroids are probably not effective. Epinephrine may be tried in severe cases, but airway intervention may be needed.

Cardiac monitoring

Cardiac monitoring in patients with severe reactions and in those with underlying cardiovascular disease is important, particularly when adrenergic agonists are used in treatment. Pulse oximetry is also useful.

Intravenous access

The IV line should be of large caliber due to the potential requirement for large-volume IV fluid resuscitation. Isotonic crystalloid solutions (ie, normal saline, Ringer lactate) are preferred. A keep-vein-open (KVO) rate is appropriate for patients with stable vital signs and only cutaneous manifestations. If hypotension or tachycardia is present, administer a fluid bolus of 20 mg/kg for children and 1 L for adults. Further fluid therapy depends on patient response. Large volumes may be required in the profoundly hypotensive patient.

Administration of Epinephrine

Epinephrine maintains blood pressure, antagonizes the effects of the released mediators, and inhibits further release of mediators. Health care professionals are sometimes reluctant to administer epinephrine for fear of adverse effects. However, the use of epinephrine for anaphylaxis has no absolute contraindications. It is the drug of choice and it is usually well tolerated and potentially lifesaving. [48, 69, 72] Anaphylactic deaths correlate with delayed administration of epinephrine. The initial dose can be repeated as necessary, depending on the response. Data are limited concerning the frequency with which patients might require repeated doses of epinephrine to treat anaphylaxis (reports range from 16-36%) and multiple cofactors might be involved. [48, 69]

Administer intramuscular (IM) epinephrine immediately. [37, 67] IM administration of epinephrine in the thigh (vastus lateralis) results in higher and more rapid maximum plasma concentrations of epinephrine than IM or subcutaneous (SC) administration in the arm (deltoid) of asymptomatic children and adults (see Medication). [49] However, similar studies comparing IM injections to SC injections in the thigh have not yet been done. Obesity or other conditions that enlarge the subcutaneous fat pad may prevent intramuscular access.

Remove the source of the antigen if possible (eg, remove stinger after honeybee sting or stop drug infusion). If anaphylaxis occurs after injection of allergen-specific subcutaneous immunotherapy (SCIT), a large local reaction often occurs. Place a tourniquet above the injection site and, after IM epinephrine is administered, inject up to 0.1 mL of epinephrine into the large local reaction site to slow absorption.

Racemic epinephrine via a nebulizer can be used to reduce laryngeal swelling, but it does not replace IM administration of epinephrine. Treat bronchospasm that has not responded to IM epinephrine with inhaled beta2 -adrenergic agonists such as albuterol.

Administration of Antihistamines and Corticosteroids

The standard treatment of anaphylaxis should also include antihistamines and corticosteroids. However, antihistamines have a much slower onset of action than epinephrine, they exert minimal effect on blood pressure, and they should not be administered alone as treatment. [73] Antihistamine therapy thus is considered adjunctive to epinephrine.

Administer an H1 blocker and an H2 blocker, because studies have shown the combination to be superior to an H1 blocker alone in relieving the histamine-mediated symptoms. Diphenhydramine and ranitidine are an appropriate combination. IV administration ensures that effective dosing is not impaired by hemodynamic compromise, which adversely affects gastrointestinal (GI) or IM absorption. However, oral or IM administration of antihistamines may suffice for milder anaphylaxis.

Corticosteroids have no immediate effect on anaphylaxis. [74] However, administer them early to try to prevent a potential late-phase reaction (biphasic anaphylaxis). Patients with asthma or other conditions recently treated with a corticosteroid may be at increased risk for severe or fatal anaphylaxis and may receive additional benefit if corticosteroids are administered to them during anaphylaxis. The authors recommend corticosteroid treatment for all patients with anaphylaxis. If absorption is a concern, IV preparations should be used.

Most patients treated with antihistamines and steroids have complete remission following tapering of steroids. Others require long-term prophylaxis with high doses of H1 antihistamines.

Outpatient medications are the oral forms of antihistamines and corticosteroids that should be continued for a short time (a few days) following an episode. The benefit of these drugs is more theoretical because no studies exist that prove their benefit in this setting.

A convenient oral corticosteroid is prednisone. No proven best dose exists. In adults, a dose of 1 mg/kg/d in divided doses is probably adequate; in children, a dose of 0.5-1 mg/kg/d in divided doses is appropriate. Tapering is not necessary unless the patient has been taking steroids chronically.

The following regimens are used commonly by clinicians, though very little hard data concerning the natural history of anaphylaxis treated in the ED exists. In light of this, do not construe the following as an unqualified recommendation or as a standard of care. Evidence for efficacy of H2 -blocker antihistamines is particularly sparse.

H1 -blocker antihistamine treatment is as follows:

• Diphenhydramine (Benadryl) - Adults: 25 mg PO q6h for 2-5 d; Children: 1 mg/kg PO q6h for 2-5 d

• Hydroxyzine (Atarax) - Adults: 25 mg PO q8h for 2-5 d; Children: 1 mg/kg PO q8h for 2-5 d

Corticosteroid treatment is as follows:

• Prednisone - Adults: 20-80 mg PO daily for 2-5 d; Children: 0.5-1 mg/kg PO daily for 2-5 d

• Many other glucocorticoid preparations may be used.

H2 -blocker antihistamine treatment is as follows:

• Cimetidine - 300 mg PO qid for 2-5 d; Children: Not recommended

Patients with frequent idiopathic anaphylaxis may benefit from daily antihistamine therapy (both H1 antagonists and H2 antagonists) or, in rare circumstances, daily corticosteroid therapy.

For daily antihistamine therapy, diphenhydramine or hydroxyzine is often used first. Second-generation, less-sedating agents may be preferable because of decreased adverse effects. In their adult doses, these include fexofenadine (Allegra) at 180 mg/d, loratadine (Claritin) at 10 mg/d, cetirizine (Zyrtec) at 10 mg/d, desloratadine (Clarinex) at 5 mg/d, and levocetirizine (Xyzal) at 5 mg/d. However, none has been specifically evaluated in anaphylaxis prevention. Some specialists prescribe extra doses of antihistamines as needed and as tolerated to control symptoms.

Management of Blood Pressure

Maintaining proper blood pressure is important in the treatment of anaphylactic reactions. Hypotension is often the most difficult manifestation of anaphylaxis to treat. Persons with protracted hypotension must be monitored in an intensive care unit (ICU) setting.

Because hypotension in anaphylaxis is due to a dramatic shift of intravascular volume, the fundamental treatment intervention after epinephrine is aggressive IV fluid administration. Large volumes of crystalloid may be required, potentially exceeding 5 L. The exact amount should be individualized and based on blood pressure and urine output. Depending on its severity, refractory hypotension may require placement of an invasive cardiovascular monitor (central venous catheter) and arterial line.

In patients with preexisting heart disease, ischemic myocardial dysfunction may occur due to hypotension and hypoxia. Epinephrine still may be necessary in patients with severe anaphylaxis, but remember the potential for exacerbating ischemia. If pulmonary congestion or evidence of cardiac ischemia is present, fluid resuscitation should be approached more cautiously.

Vasopressors may also be needed to support blood pressure. Intravenous epinephrine (1:10,000 v/v preparation) can be administered as a continuous infusion, especially when the response to intramuscular epinephrine (1:1000 v/v) is poor. Dopamine infusion can also be used.

Patients with anaphylaxis who are taking a beta-adrenergic blocking agent (eg, for hypertension, migraine prophylaxis) can have refractory anaphylaxis that is poorly responsive to standard measures. Data are limited to case reports, but glucagon might be effective in this situation. [75] It has both inotropic effects and chronotropic effects on the heart by increasing intracellular levels of cyclic adenosine 3,’5’-monophosphate, independent of the beta-adrenergic receptors. Glucagon can also reverse bronchospasm.

Treatment of Gastrointestinal Symptoms

GI symptoms in anaphylaxis may respond to H1 antihistamines and epinephrine.

Short-Term Desensitization Procedures

Short-term desensitization procedures can be used for medication allergy in some circumstances in which no therapeutic alternative exists.

Published protocols exist for short-term desensitization and are available for various medications. Consult an allergist-immunologist skilled in desensitization procedures to perform these protocols. Most protocols require the patient to be in an ICU setting throughout the procedure and to have established IV access and epinephrine at the bedside before the procedure starts. Obtain informed consent prior to the procedure. Anaphylaxis is a potential complication of this procedure.

A typical desensitization protocol for beta-lactam antibiotics provides the patient a starting dose that is 6-7 logs below the usual therapeutic dose and increases the dose by 1 log every 20-30 minutes. [76] A typical desensitization regimen involves administering the antibiotic of choice in an initial dose of 0.01 mg. While observing the patient, double the dose every 20-30 minutes until a full dose has been administered.

Desensitization regimens do not protect against non-IgE-mediated reactions that may be severe or even life threatening (eg, Stevens-Johnson syndrome).

Administration of Anti-IgE

Anti-IgE (eg, omalizumab) complexes circulating (but not receptor-bound) IgE and keeps it from binding to its receptors. It does not remove IgE bound to receptors and can take several weeks to months to have a substantial effect. It should not be used in an acute setting and would not be expected to influence IgE-independent or nonimmunologic events.

Due to the potential for delayed anaphylaxis after omalizumab (0.09% of recipients in 1 report), observation periods of 2 hours for the first 3 injections and 30 minutes for subsequent injections have been recommended. Patients should also be prescribed an epinephrine autoinjector (see above for epinephrine autoinjector instruction) and advised to carry it before omalizumab injection and for the ensuing 24 hours. [52]

Inpatient Care

The presenting manifestation(s) of anaphylaxis dictate inpatient care. Essentially, this care consists of continuing the care initiated in the ED.

Most patients with anaphylaxis may be treated successfully in the ED and then discharged. Treatment success operationally may be defined as complete resolution of symptoms followed by a short period of observation. The purpose of observation is to monitor for recurrence of symptoms (ie, biphasic anaphylaxis). An observation period of 10 hours appears sufficient for most reactions, but some investigators recommend 24 hours. [77]

Hospital admission is required for patients who (1) fail to respond fully, (2) have a recurrent reaction or a secondary complication (eg, myocardial ischemia), (3) experience a significant injury from syncope, or (4) need intubation. As with many other conditions, consider a lower admission threshold when patients are at age extremes or when they have significant comorbid illness.

Consider ICU admission for patients with persistent hypotension. The primary means of support are adrenergic agents (eg, epinephrine, dopamine) and fluid resuscitation. Persistent hypotension in the face of pressors and fluid resuscitation is an indication for invasive hemodynamic monitoring with evaluation of cardiac function and peripheral vascular resistance. Use of these parameters provides the basis for objective decisions regarding the use of fluids and pressors.

Persistent bronchospasm should be treated by continuing albuterol and intravenous steroid administration. Cutaneous manifestations of anaphylaxis are treated with repeated doses of antihistamines.

Therapy with antihistamines and oral glucocorticoids should probably continue at home for another 2-3 days to prevent recurrence.

Prevention of Anaphylaxis

Avoidance is the only form of prevention for most inciting agents. [78] Insect sting anaphylaxis can be prevented with allergen immunotherapy, which is highly effective. This recommendation is supported by updated reports of the Joint Task Force on Practice Parameters. [47, 46]

Anti-IgE may be a good prophylactic agent for severe food allergy, but the one study published to date was with TNX-901, which is not being marketed. A phase II multicenter study with omalizumab (Xolair) in peanut allergy was discontinued prematurely because of safety concerns in some study subjects. Obtained data were insufficient to draw any conclusions, but a slight trend existed toward greater tolerability of peanuts in subjects treated with omalizumab compared to placebo.

While theoretically attractive, premedication regimens have not been clinically shown to decrease incidence or severity of IgE-mediated allergic reactions to antibiotics.

Patients at risk for recurrent anaphylaxis should consider wearing a MedicAlert bracelet. [78] They should also avoid the use of beta-blockers if at all possible since this class of medication may not only increase the risk of anaphylaxis, but also block the effects of epinephrine. ACE inhibitors have also been theorized to potentially increase the risk of anaphylaxis. Tricyclic antidepressants and monoamine oxidase inhibitors should also be avoided because of potential drug interactions with necessary therapies.

Patients at risk for recurrent anaphylaxis might benefit from a written action plan. [78] The use and benefit of such plans has yet to be formally evaluated. [79, 80]

Reactions to radiocontrast media

Patients with a history of severe reactions to IV radiocontrast media may require use of contrast in an urgent or emergency situation. Alternatives (eg, noncontrast spiral computed tomography [CT] for ureteral stone, Doppler ultrasonography for deep venous thrombosis [DVT], nuclear scans or spiral CT for pulmonary embolism) should be considered but are not always feasible. In these circumstances, a prophylactic regimen of corticosteroids and antihistamines may be used.

The precise efficacy of these regimens is difficult to evaluate, but they generally are considered effective. One author states that the recurrence rate for patients with a previous reaction was reduced from 17-60% to 9% when conventional contrast material was used; the rate was reduced to less than 1% when low osmolality material was used after a pretreatment regimen.

Prophylaxis for IgE-independent anaphylactic reactions to radiocontrast media involves prednisone (or hydrocortisone), diphenhydramine, and possibly ranitidine (or another H2 antihistamine), and/or the use of a different contrast agent.

Administer prednisone (50 mg PO) or hydrocortisone (200 mg IV) at 13, 7, and 1 hour before the radiocontrast procedure.

Administer diphenhydramine (50 mg PO/IV) and ranitidine (150 mg PO or 50 mg IV) with or without ephedrine (25 mg PO) 1 hour before the procedure. Ephedrine should not be used in patients with hypertension, coronary artery disease (CAD), a strong family history of CAD (for older patients), arrhythmia, thyrotoxicosis, monoamine oxidase inhibitor use, or porphyria.

Select a radiocontrast agent with lower osmolarity.

Dietary Measures

The only dietary consideration is the future avoidance of a suspect or culprit food. Clinical trials are presently evaluating short-term oral desensitization for some foods, such as peanuts.

Consultations

Most patients with anaphylaxis should be referred to an allergist-immunologist for further evaluation and treatment. However, the Rochester County study demonstrated that 42% of patients were referred for such a consultation, [11] and emergency departments fared worse in both civilian and military settings, 12-20% and 29%, respectively.

Consultation with an allergist (when available) is appropriate when desensitization to an antibiotic is contemplated. When no inciting agent has been identified, consider referral to an allergist to identify the cause of anaphylaxis.

Some anaphylactic reactions are so severe that treatment is unsuccessful and death occurs. This underscores the critical importance of education, avoidance, and prevention. An allergist-immunologist can provide comprehensive professional advice on these matters. [78]

In the case of severe anaphylaxis requiring admission to the ICU, a critical care specialist should be consulted. When a patient at high risk for contrast reaction is under consideration for a contrast study, consultation with the radiologist regarding pretreatment and choice of contrast agent is appropriate.

Long-Term Monitoring

The most important aspect of outpatient follow-up is evaluation by an allergist-immunologist. [47, 66, 46, 48] Skin testing and/or in vitro IgE tests for foods, stinging insects, medications, or latex should be performed as directed by the patient’s history. Documented hypersensitivity to latex is an indication for evaluation of possible allergy cross-reacting foods (eg, banana, kiwi, avocado). If the patient’s history and skin test or in vitro IgE tests results confirm Hymenoptera sensitivity as the probable cause of anaphylaxis, venom-specific immunotherapy should be initiated to significantly decrease the likelihood of future episodes.

Future avoidance of culprit foods, medications, latex, or radiocontrast media must be emphasized. If a culprit medication is required in the future and no other alternatives are available, a desensitization procedure should be performed by the allergist/immunologist, usually in an ICU setting. If radiocontrast media are required in the future, a pretreatment protocol may be used. (See Prevention of Anaphylaxis.)

The patient must be provided a prescription for an epinephrine autoinjector (EpiPen, EpiPen Jr, or Twinject) and instructed in its proper use.

1. Kemp SF, Lockey RF. Anaphylaxis: a review of causes and mechanisms. J Allergy Clin Immunol. 2002 Sep. 110(3):341-8. [QxMD MEDLINE Link].

2. Simons FE. Anaphylaxis. J Allergy Clin Immunol. 2008 Feb. 121(2 Suppl):S402-7; quiz S420. [QxMD MEDLINE Link].

3. Braganza SC, Acworth JP, Mckinnon DR, Peake JE, Brown AF. Paediatric emergency department anaphylaxis: different patterns from adults. Arch Dis Child. 2006 Feb. 91(2):159-63. [QxMD MEDLINE Link]. [Full Text].

4. Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004 May. 113(5):832-6. [QxMD MEDLINE Link].

5. Finkelman FD. Anaphylaxis: lessons from mouse models. J Allergy Clin Immunol. 2007 Sep. 120(3):506-15; quiz 516-7. [QxMD MEDLINE Link].

6. Schadt JC, Ludbrook J. Hemodynamic and neurohumoral responses to acute hypovolemia in conscious mammals. Am J Physiol. 1991 Feb. 260(2 Pt 2):H305-18. [QxMD MEDLINE Link].

7. Demetriades D, Chan LS, Bhasin P, Berne TV, Ramicone E, Huicochea F, et al. Relative bradycardia in patients with traumatic hypotension. J Trauma. 1998 Sep. 45(3):534-9. [QxMD MEDLINE Link].

8. Wang J, Sampson HA. Food anaphylaxis. Clin Exp Allergy. 2007 May. 37(5):651-60. [QxMD MEDLINE Link].

9. Osborne NJ, Koplin JJ, Martin PE, et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. J Allergy Clin Immunol. 2011 Mar. 127(3):668-76.e1-2. [QxMD MEDLINE Link].

10. Hourihane JO'B, Kilburn SA, Nordlee JA, Hefle SL, Taylor SL, Warner JO. An evaluation of the sensitivity of subjects with peanut allergy to very low doses of peanut protein: a randomized, double-blind, placebo-controlled food challenge study. J Allergy Clin Immunol. 1997 Nov. 100(5):596-600. [QxMD MEDLINE Link].

11. Decker WW, Campbell RL, Manivannan V, et al. The etiology and incidence of anaphylaxis in Rochester, Minnesota: a report from the Rochester Epidemiology Project. J Allergy Clin Immunol. 2008 Dec. 122(6):1161-5. [QxMD MEDLINE Link]. [Full Text].

12. Greenhawt MJ, Li JT, Bernstein DI, et al. Administering influenza vaccine to egg allergic recipients: a focused practice parameter update. Ann Allergy Asthma Immunol. 2011 Jan. 106(1):11-6. [QxMD MEDLINE Link].

13. [Guideline] Centers for Disease Control and Prevention. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011 Aug 26. 60(33):1128-32. [QxMD MEDLINE Link].

14. Annè S, Reisman RE. Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy. Ann Allergy Asthma Immunol. 1995 Feb. 74(2):167-70. [QxMD MEDLINE Link].

15. Daulat S, Solensky R, Earl HS, Casey W, Gruchalla RS. Safety of cephalosporin administration to patients with histories of penicillin allergy. J Allergy Clin Immunol. 2004 Jun. 113(6):1220-2. [QxMD MEDLINE Link].

16. Lin RY. A perspective on penicillin allergy. Arch Intern Med. 1992 May. 152(5):930-7. [QxMD MEDLINE Link].

17. Pichichero ME. A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics. 2005 Apr. 115(4):1048-57. [QxMD MEDLINE Link].

18. Mertes PM, Malinovsky JM, Jouffroy L, et al. Reducing the risk of anaphylaxis during anesthesia: 2011 updated guidelines for clinical practice. J Investig Allergol Clin Immunol. 2011. 21(6):442-53. [QxMD MEDLINE Link].

19. Golden DB. Insect sting anaphylaxis. Immunol Allergy Clin North Am. 2007 May. 27(2):261-72, vii. [QxMD MEDLINE Link]. [Full Text].

20. Amin HS, Liss GM, Bernstein DI. Evaluation of near-fatal reactions to allergen immunotherapy injections. J Allergy Clin Immunol. 2006 Jan. 117(1):169-75. [QxMD MEDLINE Link].

21. Bernstein DI, Wanner M, Borish L, Liss GM. Twelve-year survey of fatal reactions to allergen injections and skin testing: 1990-2001. J Allergy Clin Immunol. 2004 Jun. 113(6):1129-36. [QxMD MEDLINE Link].

22. Lockey RF, Benedict LM, Turkeltaub PC, Bukantz SC. Fatalities from immunotherapy (IT) and skin testing (ST). J Allergy Clin Immunol. 1987 Apr. 79(4):660-77. [QxMD MEDLINE Link].

23. Greenberger PA. Idiopathic anaphylaxis. Immunol Allergy Clin North Am. 2007 May. 27(2):273-93, vii-viii. [QxMD MEDLINE Link].

24. Meggs WJ, Pescovitz OH, Metcalfe D, Loriaux DL, Cutler G Jr, Kaliner M. Progesterone sensitivity as a cause of recurrent anaphylaxis. N Engl J Med. 1984 Nov 8. 311(19):1236-8. [QxMD MEDLINE Link].

25. Slater JE, Raphael G, Cutler GB Jr, Loriaux DL, Meggs WJ, Kaliner M. Recurrent anaphylaxis in menstruating women: treatment with a luteinizing hormone-releasing hormone agonist--a preliminary report. Obstet Gynecol. 1987 Oct. 70(4):542-6. [QxMD MEDLINE Link].

26. Lieberman P. Anaphylaxis. Adkinson NF Jr, Bochner BS, Busse, WW, Holgate ST, Lemanske RF Jr, Simons FER, eds. Middleton’s Allergy: Principles and Practice. 7th. Philadelphia, Pa: Elsevier; 2009. 1027-49.

27. Stark BJ, Sullivan TJ. Biphasic and protracted anaphylaxis. J Allergy Clin Immunol. 1986 Jul. 78(1 Pt 1):76-83. [QxMD MEDLINE Link].

28. Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med. 1992 Aug 6. 327(6):380-4. [QxMD MEDLINE Link].

29. Webb LM, Lieberman P. Anaphylaxis: a review of 601 cases. Ann Allergy Asthma Immunol. 2006 Jul. 97(1):39-43. [QxMD MEDLINE Link].

30. Boggs W. Anaphylaxis worse with antihypertensive medication. Medscape Medical News. March 21, 2013. Available at http://www.medscape.com/viewarticle/781274. Accessed: April 2, 2013.

31. Lee S, Hess EP, Nestler DM, Bellamkonda Athmaram VR, Bellolio MF, Decker WW, et al. Antihypertensive medication use is associated with increased organ system involvement and hospitalization in emergency department patients with anaphylaxis. J Allergy Clin Immunol. 2013 Apr. 131(4):1103-8. [QxMD MEDLINE Link].

32. Lieberman P. Epidemiology of anaphylaxis. Curr Opin Allergy Clin Immunol. 2008 Aug. 8(4):316-20. [QxMD MEDLINE Link].

33. Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med. 2001 Jan 8. 161(1):15-21. [QxMD MEDLINE Link].

34. Bresser H, Sandner CH, Rakoski J. Anaphylactic emergencies in Munich in 1992 (abstract). J Allergy Clin Immunol. Jan 1995. 95:368.

35. Mertes PM, Laxenaire MC, Alla F. Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000. Anesthesiology. 2003 Sep. 99(3):536-45. [QxMD MEDLINE Link].

36. Simons FE, Sampson HA. Anaphylaxis epidemic: fact or fiction?. J Allergy Clin Immunol. 2008 Dec. 122(6):1166-8. [QxMD MEDLINE Link].

37. Simons FE, Peterson S, Black CD. Epinephrine dispensing patterns for an out-of-hospital population: a novel approach to studying the epidemiology of anaphylaxis. J Allergy Clin Immunol. 2002 Oct. 110(4):647-51. [QxMD MEDLINE Link].

38. Moneret-Vautrin DA, Morisset M, Flabbee J, Beaudouin E, Kanny G. Epidemiology of life-threatening and lethal anaphylaxis: a review. Allergy. 2005 Apr. 60(4):443-51. [QxMD MEDLINE Link].

39. Bock SA, Muñoz-Furlong A, Sampson HA. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001 Jan. 107(1):191-3. [QxMD MEDLINE Link].

40. Greenberger PA, Rotskoff BD, Lifschultz B. Fatal anaphylaxis: postmortem findings and associated comorbid diseases. Ann Allergy Asthma Immunol. 2007 Mar. 98(3):252-7. [QxMD MEDLINE Link].

41. Shehadi WH. Adverse reactions to intravascularly administered contrast media. A comprehensive study based on a prospective survey. Am J Roentgenol Radium Ther Nucl Med. 1975 May. 124(1):145-52. [QxMD MEDLINE Link].

42. Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media. Radiology. 1990 Jun. 175(3):621-8. [QxMD MEDLINE Link].

43. Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. J Allergy Clin Immunol. 1991 Apr. 87(4):867-72. [QxMD MEDLINE Link].

44. Pumphrey RS. Fatal posture in anaphylactic shock. J Allergy Clin Immunol. 2003 Aug. 112(2):451-2. [QxMD MEDLINE Link].

45. Demuth KA, Fitzpatrick AM. Epinephrine autoinjector availability among children with food allergy. Allergy Asthma Proc. 2011 Jul. 32(4):295-300. [QxMD MEDLINE Link].

46. [Guideline] Golden DB, Moffitt J, Nicklas RA, Freeman T, Graft DF, Reisman RE, et al. Stinging insect hypersensitivity: a practice parameter update 2011. J Allergy Clin Immunol. 2011 Apr. 127(4):852-4.e1-23. [QxMD MEDLINE Link].

47. Lieberman P, Nicklas RA, Randolph C, Oppenheimer J, Bernstein D, et al. Anaphylaxis--a practice parameter update 2015. Ann Allergy Asthma Immunol. 2015 Nov. 115 (5):341-84. [QxMD MEDLINE Link].

48. [Guideline] Simons FE, Ardusso LR, Dimov V, Ebisawa M, El-Gamal YM, Lockey RF, et al. World Allergy Organization Anaphylaxis Guidelines: 2013 update of the evidence base. Int Arch Allergy Immunol. 2013. 162 (3):193-204. [QxMD MEDLINE Link].

49. Haymore BR, Carr WW, Frank WT. Anaphylaxis and epinephrine prescribing patterns in a military hospital: underutilization of the intramuscular route. Allergy Asthma Proc. 2005 Sep-Oct. 26(5):361-5. [QxMD MEDLINE Link].

50. Rosen JP. Empowering patients with a history of anaphylaxis to use an epinephrine autoinjector without fear. Ann Allergy Asthma Immunol. 2006 Sep. 97(3):418. [QxMD MEDLINE Link].

51. Soller L, Fragapane J, Ben-Shoshan M, et al. Possession of epinephrine auto-injectors by Canadians with food allergies. J Allergy Clin Immunol. 2011 Aug. 128(2):426-8. [QxMD MEDLINE Link].

52. Cox L, Platts-Mills TA, Finegold I, Schwartz LB, Simons FE, Wallace DV. American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis. J Allergy Clin Immunol. 2007 Dec. 120(6):1373-7. [QxMD MEDLINE Link].

53. Limb SL, Starke PR, Lee CE, Chowdhury BA. Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma. J Allergy Clin Immunol. 2007 Dec. 120(6):1378-81. [QxMD MEDLINE Link].

54. Cheifetz A, Smedley M, Martin S, et al. The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenterol. 2003 Jun. 98(6):1315-24. [QxMD MEDLINE Link].

55. Stallmach A, Giese T, Schmidt C, Meuer SC, Zeuzem SS. Severe anaphylactic reaction to infliximab: successful treatment with adalimumab - report of a case. Eur J Gastroenterol Hepatol. 2004 Jun. 16(6):627-30. [QxMD MEDLINE Link].

56. Commins SP, Platts-Mills TA. Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant. J Allergy Clin Immunol. 2009 Oct. 124(4):652-7. [QxMD MEDLINE Link]. [Full Text].

57. Smith PL, Kagey-Sobotka A, Bleecker ER, et al. Physiologic manifestations of human anaphylaxis. J Clin Invest. 1980 Nov. 66(5):1072-80. [QxMD MEDLINE Link]. [Full Text].

58. van der Linden PW, Struyvenberg A, Kraaijenhagen RJ, Hack CE, van der Zwan JK. Anaphylactic shock after insect-sting challenge in 138 persons with a previous insect-sting reaction. Ann Intern Med. 1993 Feb 1. 118(3):161-8. [QxMD MEDLINE Link].

59. Brown SG, Blackman KE, Stenlake V, Heddle RJ. Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation. Emerg Med J. 2004 Mar. 21(2):149-54. [QxMD MEDLINE Link]. [Full Text].

60. Akin C. Anaphylaxis and mast cell disease: what is the risk?. Curr Allergy Asthma Rep. 2010 Jan. 10(1):34-8. [QxMD MEDLINE Link].

61. Bonadonna P, Perbellini O, Passalacqua G, et al. Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol. 2009 Mar. 123(3):680-6. [QxMD MEDLINE Link].

62. Rueff F, Przybilla B, Bilo MB, et al. Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase-a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity. J Allergy Clin Immunol. 2009 Nov. 124(5):1047-54. [QxMD MEDLINE Link].

63. Lin RY, Schwartz LB, Curry A, Pesola GR, Knight RJ, Lee HS, et al. Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based study. J Allergy Clin Immunol. 2000 Jul. 106(1 Pt 1):65-71. [QxMD MEDLINE Link].

64. Simons FE. Anaphylaxis pathogenesis and treatment. Allergy. 2011 Jul. 66 Suppl 95:31-4. [QxMD MEDLINE Link].

65. Vadas P, Gold M, Perelman B, et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med. 2008 Jan 3. 358(1):28-35. [QxMD MEDLINE Link].

66. [Guideline] Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol. 2010 Dec. 126(6 Suppl):S1-58. [QxMD MEDLINE Link].

67. Lieberman P. Use of epinephrine in the treatment of anaphylaxis. Curr Opin Allergy Clin Immunol. 2003 Aug. 3(4):313-8. [QxMD MEDLINE Link].

68. Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: summary report--second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. Ann Emerg Med. 2006 Apr. 47(4):373-80. [QxMD MEDLINE Link].

69. Kemp SF, Lockey RF, Simons FE. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy. 2008 Aug. 63(8):1061-70. [QxMD MEDLINE Link].

70. Laidman J. Anaphylaxis requires prompt epinephrine shot. Medscape Medical News. December 3, 2014. [Full Text].

71. [Guideline] Campbell RL, Li JT, Nicklas RA, Sadosty AT. Emergency department diagnosis and treatment of anaphylaxis: a practice parameter. Ann Allergy Asthma Immunol. 2014 Dec. 113(6):599-608. [QxMD MEDLINE Link].

72. Sheikh A, Shehata YA, Brown SG, Simons FE. Adrenaline for the treatment of anaphylaxis: cochrane systematic review. Allergy. 2009 Feb. 64(2):204-12. [QxMD MEDLINE Link].

73. Sheikh A, Ten Broek V, Brown SG, Simons FE. H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review. Allergy. 2007 Aug. 62(8):830-7. [QxMD MEDLINE Link].

74. Choo KJ, Simons E, Sheikh A. Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy. 2010 Oct. 65(10):1205-11. [QxMD MEDLINE Link].

75. Thomas M, Crawford I. Best evidence topic report. Glucagon infusion in refractory anaphylactic shock in patients on beta-blockers. Emerg Med J. 2005 Apr. 22(4):272-3. [QxMD MEDLINE Link]. [Full Text].

76. Borish L, Tamir R, Rosenwasser LJ. Intravenous desensitization to beta-lactam antibiotics. J Allergy Clin Immunol. 1987 Sep. 80(3 Pt 1):314-9. [QxMD MEDLINE Link].

77. Kemp SF. The post-anaphylaxis dilemma: how long is long enough to observe a patient after resolution of symptoms?. Curr Allergy Asthma Rep. 2008 Mar. 8(1):45-8. [QxMD MEDLINE Link].

78. Simons FE. Anaphylaxis: evidence-based long-term risk reduction in the community. Immunol Allergy Clin North Am. 2007 May. 27(2):231-48, vi-vii. [QxMD MEDLINE Link].

79. Nurmatov U, Worth A, Sheikh A. Anaphylaxis management plans for the acute and long-term management of anaphylaxis: a systematic review. J Allergy Clin Immunol. 2008 Aug. 122(2):353-61, 361.e1-3. [QxMD MEDLINE Link].

80. Choo K, Sheikh A. Action plans for the long-term management of anaphylaxis: systematic review of effectiveness. Clin Exp Allergy. 2007 Jul. 37(7):1090-4. [QxMD MEDLINE Link].

81. Alrasbi M, Sheikh A. Comparison of international guidelines for the emergency medical management of anaphylaxis. Allergy. 2007 Aug. 62(8):838-41. [QxMD MEDLINE Link].

82. Johnson K. Antibiotics common cause of perioperative anaphylaxis. Medscape Medical News. November 22, 2013. [Full Text].

Author

S Shahzad Mustafa, MD Physician in Allergy, Immunology, and Rheumatology, Rochester General Medical Group; Clinical Assistant Professor of Medicine, University of Rochester School of Medicine and Dentistry

S Shahzad Mustafa, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, Finger Lakes Allergy Society

Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians

Disclosure: Nothing to disclose.

Acknowledgements

Roy Alson, MD, PhD, FACEP, FAAEM Associate Professor, Department of Emergency Medicine, Wake Forest University School of Medicine; Medical Director, Forsyth County EMS; Deputy Medical Advisor, North Carolina Office of EMS; Associate Medical Director, North Carolina Baptist AirCare

Roy Alson, MD, PhD, FACEP, FAAEM is a member of the following medical societies: Air Medical Physician Association, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, National Association of EMS Physicians, North Carolina Medical Society, Society for Academic Emergency Medicine, and World Association for Disaster and Emergency Medicine

Disclosure: Nothing to disclose.

Stephen C Dreskin, MD, PhD Professor of Medicine, Departments of Internal Medicine, Director of Allergy, Asthma, and Immunology Practice, University of Colorado Health Sciences Center

Stephen C Dreskin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association for the Advancement of Science, American Association of Immunologists, American College of Allergy, Asthma and Immunology, Clinical Immunology Society, and Joint Council of Allergy, Asthma and Immunology

Disclosure: Genentech Consulting fee Consulting; American Health Insurance Plans Consulting fee Consulting; Johns Hopkins School of Public Health Consulting fee Consulting; Array BioPharma Consulting fee Consulting

Stephen F Kemp, MD, FACP Professor of Medicine, Associate Professor of Pediatrics, Director of Allergy and Immunology Fellowship Program, Departments of Medicine and Pediatrics, Associate Director of Division of Clinical Immunology and Allergy, Department of Medicine, University of Mississippi Medical Center; Staff Physician and Consultant in Allergy and Immunology, Medical Service, G V (Sonny) Montgomery Veterans Affairs Medical Center

Stephen F Kemp, MD, FACP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Physicians, Association of Subspecialty Professors, Joint Council of Allergy, Asthma and Immunology, Mississippi State Medical Association, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Richard S Krause, MD Senior Clinical Faculty/Clinical Assistant Professor, Department of Emergency Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

G William Palmer, MD Consulting Staff, Shoreline Allergy and Asthma Associates

G William Palmer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Matthew M Rice, MD, JD, FACEP Senior Vice President, Chief Medical Officer, Northwest Emergency Physicians of TeamHealth; Assistant Clinical Professor of Medicine, University of Washington School of Medicine

Matthew M Rice, MD, JD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, National Association of EMS Physicians, Society for Academic Emergency Medicine, and Washington State Medical Association

Disclosure: Team Health Salary Employment

Erik D Schraga, MD Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

What is the only treatment for anaphylaxis?

How do hospitals respond to anaphylaxis?

What do they do in ER for allergic reaction?