OBJECTIVES
1. To recognize anaphylaxis
2. To consider the differential diagnosis of anayphylaxis
3. To understand the basic pathophysiology of anaphylaxis
4. To review the management of anaphylaxis 5. To provide the appropriate discharge instructions
for patients with anaphylaxis
INTRODUCTION
Anaphylaxis is a common and potentially life- threatening emergency. Anaphylactic reactions vary dramatically, from simple cutaneous reactions, to respiratory and cardiovascular compromise and death. While only 500-1500 fatal anaphylactic reactions occur annually in the United States, a significant proportion of the population is at risk for these reactions. With appropriate, early treatment and effective prevention strategies, the risk of morbidity and mortality from anaphylaxis can be diminished.
PRESENTATION
Due to the highly variable nature of anaphylaxis, a clear definition is difficult to attain. All definitions are flawed in some respect. One recent article uses the following useful definition: ―Anaphylaxis is a severe allergic reaction to any stimulus, (usually) having sudden onset and generally lasting less than 24 hours, involving one or more body systems and producing one or more symptoms such as hives, flushing, itching, angioedema, stridor, wheezing, shortness of breath, vomiting, diarrhea, or shock‖. Symptom onset varies widely, but commonly occurs seconds to minutes after exposure. Occasionally, symptom onset may take several hours.
Differential Diagnosis
The majority of cases of anaphylaxis are quite straightforward and obvious to diagnose. A history of prior allergy and exposure to an offending agent followed by the development of mucocutanous signs often assist in the diagnosis of anaphylaxis.
However, in patients with no previous history of allergy, or those who present with only respiratory, gastrointestinal, or cardiovascular compromise, the diagnosis of anaphylaxis becomes clinically
challenging. There are no laboratory tests that aid in the diagnosis of anaphylaxis in the acute setting. A differential diagnosis depends on the predominant presenting symptom.
Patients presenting with hypotension or shock should be examined to exclude septic shock, cardiogenic shock, hypovolemic shock, pulmonary embolism, tension pneumothorax, cardiac tamponade and vasovagal reactions. The differential diagnosis for respiratory distress includes: asthma, COPD, foreign body aspiration, and vocal cord dysfunction. Patients presenting with anaphylaxis have been misdiagnosed as being anxious or having a panic attack, leading to delays in treatment and morbidity.
Epidemiology and Causative Agents
Limited data is available on the incidence of anaphylaxis in Canada or elsewhere. It is widely considered to be under reported and under recognized. Approximately 1 in every 1000-3000 patient visits to an emergency department is due to an anaphylactic reaction. Anaphylaxis leads to
approximately 500-1500 deaths annually in the
Frequency of Signs and symptoms
Signs and symptoms Frequency (%)
urticaria, angioedema 88
dyspnea, wheeze 47
dizziness, syncope, hypotension 33 nausea, vomiting, diarrhea, cramping
abdominal pain
30
flush 46
upper airway edema 56
headache 15
rhinitis 16
substernal pain 6
pruritis without rash 4.5
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months.
Food allergy is the most common cause of
anaphylaxis in North America and Western Europe. 1-2% of Americans are reported to have a food allergy, with 100 food related anaphylactic fatalities reported annually. The most common allergens are peanuts, tree nuts, shellfish, fish, milk, eggs, soy and wheat. Peanuts and tree nuts (cashew, hazelnut, walnut) account for well over half of all food allergies in the United States. There has been a dramatic increase in the prevalence of food related allergy in the United States over the past 2-3 decades. It is hypothesized that the widespread use of peanuts in processed food supplies, leading to earlier and more extensive exposure to these allergens, may account for some of the rise in prevalence of these allergies. A history of asthma or atopy is a risk factor for
development of severe food related anaphylactic reactions.
Iatrogenically induced anaphylactic reactions are the second most common cause of anaphylaxis and the leading cause of anaphylactic fatalities. 2-3% of hospitalized patients will have an allergic reaction from a drug given in hospital. 56% of iatrogenic anaphylaxis will occur while in the operating room. Fatal iatrogenic anaphylactic reactions tend to occur very rapidly, with cardiac arrest occurring in less than 5 minutes in the majority of cases. It is imperative that all health care professionals be familiar with the prompt diagnosis and treatment of anaphylactic reactions. Parenteral drugs tend to lead to more severe and more rapidly developing reactions. The most common drugs causing anaphylactic reactions are antibiotics, with penicillin alone accounting for 75% of all fatal anaphylactic reactions. Other - lactam antibiotics, radiocontrast media, ASA, IV anaesthetics, NSAIDS and opioids are also common causes of iatrogenic anaphylaxis.
Insect stings are another common cause of anaphylactic reactions. 0.5-2% of the American population have a sting allergy, with sting induced anaphylaxis accounting for 40-100 deaths annually in the United States. The risk of recurrence after an episode of sting-induced anaphylaxis is 30-60%. Latex has recently become a significant allergen causing anaphylaxis. It is estimated that while only 1- 2% of the general public has a latex sensitivity, 8- 17% of health care works are latex sensitive.
Pathophysiology
Acute anaphylaxis is an IgE-mediated allergic phenomenon. Allergic anaphylaxis requires prior exposure and sensitization to an allergen. Upon
subsequent exposure, the allergen is recognized and a reaction is triggered. A recognized allergen will bind IgE on the surface of mast cells and plasma basophils, causing them to degranulate and release histamine and other bioactive mediators. Closely related to anaphylaxis, anaphylactoid reactions similarly cause degranulation of mast cells and basophils in a non- IgE mediated cascade. Anaphylactoid reactions are clinically indistinguishable from anaphylaxis and are treated in an identical manner.
Histamine activates H1 and H2 receptors. Pruritis, rhinorrhea, tachycardia, and bronchospasm are caused by activation of H1 receptors. H1 and H2 receptors both mediate headache, flushing and hypotension. Many of histamine‘s effects can be traced to increased capillary permeability and vasodilation. In the skin, this leads to urticaria. In subcutaneous tissue, this causes angioedema. System wide vasodilation causes hypotension and shock, while increased inflammation in the respiratory and gastrointestinal systems lead to dyspnea, wheezing, vomiting, diarrhea, and crampy abdominal pain.
MANAGEMENT
As with all potential life threatening emergencies, special focus should initially be placed on management of the ABC‘s. All patients should be placed in a closely-observed setting with continuous O2 saturation and cardiac monitoring.
Emergency airway management in severe anaphylaxis can pose significant problems. In cases of significant airway edema, or intractable wheezing, orotracheal intubation should be initiated. If difficulty is expected due to obstructive airway edema, one can attempt awake fibreoptic intubation, but the patient (and physician) should be prepared for an emergency surgical airway.
Breathing should be augmented with 100% O2 via nonrebreathing mask. An inhaled 2 agonist should be given to wheezing patients. Intravenous access should be obtained in all patients. In cases of hypotension and shock, rapid infusions of 1–2 L of crystalloid (20cc/kg in children) should be started. Due to the rarity and incidental nature of anaphylaxis, little high grade evidence regarding treatment is available. The majority of treatment
recommendations are based on consensus opinion. The mainstay of pharmacologic treatment of anaphylaxis is epinephrine. Because subcutaneous administration leads to localized vasoconstriction and decreased plasma uptake of epinephrine, an
All contents copyright © 2012, University of Toronto. All rights reserved intramuscular route is the preferred method of
administration. The dose of epinephrine in anaphylaxis is 0.3–0.5 mg IM (0.01 mg/kg in children) of 1:1000. Epinephrine acts on receptors, causing vasoconstriction, leading to an increase in blood pressure and a decrease in angioedema. Its effects on bronchial 2 receptors causes
bronchodilation, while excitation of 2 receptors on mast cell and basophils lead to a decrease in the release of inflammatory mediators. Patients with a history of cardiac ischemia should be closely watched, but there is no absolute contraindication to the use of epinephrine in anaphylaxis. Medications that may increase the effect of epinephrine include MAOIs and some TCAs.
Patients on -blockers may not respond to
epinephrine. If hypotension persists in these patients, one should administer glucagon 1 mg IV, in repeat doses every 5 minutes (max 10 doses). If bolus administration is successful, a glucagon infusion should be started at 1–5 mg/hr.
As histamine is the prime mediator of anaphylaxis, antihistamines should be administered. An H1 receptor blocker such as dyphenhydramine 50 mg IV (1 mg/kg) and an H2 receptor blocker such as ranitidine 50mg (1 mg/kg) IV should both be given. Although not effective in the acute phase of an anaphylactic reaction, corticosteroids may play a role in minimizing the chance of a second phase reaction. Some patients may improve dramatically after initial therapy, only to have a recurrence of severe
symptoms 4-12 hours later. A dose of steroid (e.g. Methylpredinsone 1 mg/kg IV) is thought to reduce the possibility of a second phase reaction.
In cases of severe refractory hypotension, IV epinephrine should be carefully administered in a monitored setting. Doses should be titrated up from 0.01 g/kg/min up to 1 g/kg/min. The addition of other vasopressors may be required.
DISPOSITION
Instructions and Follow-Up
All patients should be monitored in the emergency department for a minimum of 4-6 hours due to the risk of a second phase, or rebound reaction. Second phase reactions have been reported up to 24 hours after initial exposure. All patients discharged from hospital should be supervised and have ready access to emergency services (911).
There is no clear evidence guiding ongoing treatment with medications after hospital discharge. It is common practice to treat most patients with a non- sedating H1 antagonist antihistamine (e.g. Certrizine 10mg po od), an H2 antagonist (e.g. Ranitidine 150mg po bid) and a corticosteroid (e.g. Prednisone 50mg po od) each for a 3 day course.
All patients who have had a significant anaphylactic reaction should be prescribed an automated self- injectable epinephrine device (e.g. Epipen) and instructed on its use. Patients should be instructed to carry the device on their person at all times.
Discharge
An Epipen contains 0.3mg of 1:1000 epinephrine that should be delivered IM into the lateral aspect of the thigh (vastus lateralis), through clothing if necessary. Epipen Jr. (0.15mg of epinephrine) should be prescribed to children weighing 10-25 kg and parents should be instructed on its use. Children weighing less than 10 kg pose a special risk, as no automated administration device is available in low doses. Parents should be instructed on how to draw up and administer 1:1000 epinephrine at an appropriate dose.
In addition to epinephrine, the patient may be instructed on self administration of an oral
antihistamine (e.g. diphenhydramine 50 mg) in liquid form in the event of a recurrent exposure. All patients should be instructed to seek immediate medical attention in an ER during an allergic reaction, even when treatment has been self initiated.
In cases when an offending allergen is identified, patients should be instructed on strict avoidance of the allergen. Avoidance is the only way to prevent future reactions, although accidental exposures occur in some instances.
A medic-alert or similar identification bracelet should be suggested in case of future exposure. Some physicians suggest that an anaphylaxis emergency plan, containing a photo ID and list of triggers, be given to school offices or workplaces for patients
CLINICAL PEARLS
Some patients with anaphylaxis may improve dramatically after initial therapy, only to have a recurrence of severe symptoms 4-12 hours later. A dose of steroid is thought to reduce the possibility of a second phase reaction.
All contents copyright © 2012, University of Toronto. All rights reserved with severe anaphylaxis. Education of family and
close friends may play a role in the early management of severe cases. A referral to an allergy specialist for further education and skin-prick testing in patients without an identifiable cause has been proven to be beneficial.
Patients with insect sting allergy should be referred to an allergy specialist for immunotherapy.
Immunotherapy in these reactions can reduce
recurrence rates of severe reactions to insect stings by 97%. Desensitization protocols are also available for some antibiotics including penicillin.
SUMMARY
Anaphylaxis is a multisystem disease Although anaphylaxis is common, fatal
anaphylaxis is very uncommon
Prompt recognition and treatment is vital Epinephrine (0.01 mg/kg IM) is the mainstay of
treatment
Discharge instructions should be reviewed to reduce the chances of recurrent severe anaphylaxis
REFERENCES
1. Ellis AK, Day JH. Diagnosis and management of anaphylaxis. CMAJ 2003; 169(4):307-12. 2. Sampson HA. Anaphylaxis and emergency treatment. Pediatrics 2003; 111:1601-08. 3. Tang AW. A practical guide to anaphylaxis. Am
Fam Physician 2003; 68:1325-32, 1339-40. 4. Langran M, Laird C. Management of allergy,
rashes and itching. Emerg Med J 2004; 21:728- 41.
5. Tintinalli J et al, editors. Emergency Medicine: A Comprehensive Study Guide. 7th edition. New York: McGraw Hill, 2011.
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Pharmacologic Treatment for Acute Anaphylaxis
Drug Dose / Route Indication
epinephrine 0.3 – 0.5 mg IM (0.01 mg/kg (1:1000) IM) hypotension, angioedema, wheezing IV Crystalloid 1 – 2 L IV (10 – 20 cc/kg) hypotension dyphenhydramine 50 mg IV (1 mg/kg IV)
pruritis, urticaria, wheezing, angioedema
ranitidine 50 mg IV
(1 mg/kg IV)
pruritis, urticaria, wheezing, angioedema methylprednisone 80 – 125 mg IV (1 – 2 mg/kg IV) hypotension, angioedema, wheezing salbutamol 5 mg in 3 cc NS inhaled (0.15 mg/kg inhaled) bronchospasm glucagon 1 mg IV bolus 1 – 5 mg/hr IV infusion
refractory hypotension with - blockers
aminophylline 5 mg/kg bolus over 20 min then 0.8 mg/kg/hr
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