2. Presented by: M.Rezai EM Physician IUMS

3. Anaphylaxis is a medical emergency that requires immediate diagnosis and treatment. 1. Acute onset of an illness (minutes to several hours) with involvement of the skin and/or mucosal tissue (e.g., hives/urticaria, pruritus, flushing, swollen lips, tongue, or uvula) associated with at least one of the following: Respiratory compromise (e.g., dyspnea, wheeze, stridor, etc.) or Reduced blood pressure or Associated symptoms of organ dysfunction (e.g., hypotonia, syncope, incontinence, etc.) 2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours): Involvement of the skin and/or mucosal tissue Respiratory compromise Reduced blood pressure or associated symptoms Persistent GI symptoms (e.g., cramps, vomiting) 3. Anaphylaxis should be suspected when patients are exposed to a known allergen and develop hypotension

4. Hypersensitivity is an inappropriate immune response to generally harmless antigens. Anaphylaxis represents the most dramatic and severe form of immediate hypersensitivity. Anaphylaxis occurs as part of a clinical continuum. It can begin with relatively minor symptoms and rapidly progress to a life- threatening respiratory and cardiovascular reaction.

5. Epidemiology Foods, medications, insect stings, and allergen immunotherapy injections are the most common provoking factor. Β-Lactam antibiotics are estimated to cause 400 to 800 deaths in the U.S. annually, with a systemic allergic reaction occurring in 1 per 10,000 exposures. Unavoidable

6. Drugs -Lactam antibiotics Acetylsalicylic acid Trimethoprim-sulfamethoxazole Vancomycin NSAIDs Virtually any drug Foods and additives Shellfish Soybeans Nuts (peanuts and tree nuts) Wheat Milk Eggs Salicylates Seeds Sulfites Others Hymenoptera stings Insect parts and molds Radiographic contrast material Vaccines Latex

7. Clinical Features Diffuse urticaria and angioedema Abdominal pain or cramping, nausea, vomiting, diarrhea, bronchospasm, rhinorrhea, conjunctivitis, dysrhythmias, and/or hypotension. Even mild, localized urticaria can progress to full anaphylaxis, and even to death.

8. Clinical Features The classic presentation of anaphylaxis begins with pruritus, cutaneous flushing, and urticaria. These symptoms are followed by a sense of fullness in the throat, anxiety, a sensation of chest tightness, shortness of breath, and lightheadedness. As the cascade progresses, decreased level of consciousness, respiratory distress, and circulatory collapse may ensue. A complaint of a "lump in the throat" and hoarseness heralds life- threatening laryngeal edema in a patient with symptoms of anaphylaxis.

9. Clinical Features In the vast majority of patients, signs and symptoms begin suddenly, often within 60 minutes of exposure. One half of anaphylactic fatalities occur within the first hour. Recurrence: The exact incidence of biphasic phenomenon is unclear, although it has been reported in 3% to 20% of patients. 10 (3 to 4 hours after the initial clinical manifestations have cleared).

10. Diagnosis The diagnosis of anaphylaxis is clinical. Anaphylaxis should be considered when involvement of any two or more body systems is observed, with or without hypotension or airway compromise (e.g., some combination of cutaneous, respiratory, GI, or cardiovascular systems)

11. Diagnosis Respiratory: Rhinitis, pharyngeal edema, laryngeal edema, cough, bronchospasm, dyspnea Cardiovascular: Dysrhythmias, collapse, cardiac arrest Skin: Pruritus, urticaria, angioedema, flushing GI: Nausea, emesis, cramps, diarrhea Eye: Pruritus, tearing, redness GU: Urgency, cramps

12. Treatment

13. Emergency Treatment Triage: the highest level of urgency The single most important step in treatment is the rapid administration of epinephrine Many of the secondary measures may not be necessary.

14. First-Line Therapy ABCs (airway, breathing, circulation) The first-line therapies for anaphylaxis: Epinephrine, IV fluids, and oxygen Vital signs, IV access, oxygen administration, cardiac monitoring, and pulse oximetry measurements should be initiated immediately.

15. Airway and Oxygenation The airway should be examined for signs and symptoms of angioedema (e.g., uvula edema, audible stridor, respiratory distress, hypoxia). If angioedema is producing respiratory distress, intubation should be completed early The patient should be given sufficient oxygen to maintain arterial oxygen saturation >90%.

16. Decontamination Terminate exposure to the causative agent Gastric lavage is not recommended for food- borne allergens. In insect stings, as the stinger continues to inject venom even if it is detached from the insect, remove any stinging remnants

17. Epinephrine Epinephrine is the drug of choice and the first drug that should be administered in acute anaphylaxis. α1 & β2 receptor agent α1 activation: reduces mucosal edema and membrane leakage and treats hypotension β2 activation: bronchodilation and controls mediator release

18. Epinephrine In patients without signs of cardiovascular compromise or collapse: IM epinephrine 0.3 to 0.5 milligram (0.3 to 0.5 mL of the 1:1000 dilution) IM repeated every 5 to 10 minutes according to response or relapse. EpiPen ® (0.3 milligram epinephrine for adults) and EpiPen Junior ® (0.15 milligram epinephrine for children <30 kg).

19. Epinephrine If the patient is refractory to treatment despite repeated IM epinephrine, or with signs of cardiovascular compromise or collapse: IV infusion of epinephrine. 100 micrograms (0.1 milligram) IV, should be given as a 1:100,000 dilution. 0.1 milligram (0.1 mL of the 1:1000 dilution), in 10 mL of normal saline (NS) solution and infusing it over 5 to 10 minutes (a rate of 1 to 2 mL/min). If the patient is refractory to the initial bolus, then an epinephrine infusion can be started by placing epinephrine, 1 milligram (1.0 mL of the 1:1000 dilution), in 500 mL of 5% dextrose in water or NS and administering at a rate of 1 to 4 micrograms/min (0.5 to 2 mL/min), titrating to effect.

20. Crystalloids If hypotension is present, it is generally the result of distributive shock and responds to fluid resuscitation. NS bolus of 1 to 2 L (10 to 20 mL/kg in children) concurrently with the epinephrine infusion. There is no evidence that albumin or hypertonic saline should replace NS at this time

21. Second-Line Therapy Corticosteroids Antihistamines Asthma medications Glucagon.

22. Corticosteroids Methylprednisolone: 80 to 125 milligrams IV (2 milligrams/kg in children; up to 125 milligrams) Hydrocortisone: 250 to 500 milligrams IV (5 to 10 milligrams/kg in children; up to 500 milligrams) Methylprednisolone produces less fluid retention than hydrocortisone and is preferred for elderly patients and for those patients in whom fluid retention would be problematic (e.g., renal and cardiac impairment).

23. Antihistamines All patients with anaphylaxis should receive a histamine-1 blocker, such as diphenhydramine, 25 to 50 milligrams IV. It is recommended that histamine-2 blockers, such as ranitidine or cimetidine, be given as well After the initial IV dose of steroids and antihistamines, the patient may be switched to oral medication

24. Agents for Allergic Bronchospasm If wheezing is present: intermittent or continuous nebulized albuterol/salbutamol Anticholinergics: ipratropium bromide, 250 to 500 micrograms/dose Magnesium sulfate: 2 grams IV over 20 to 30 minutes in adults and 25 to 50 milligrams/kg in children.

25. Glucagon Patients taking β-blockers with hypotension refractory to fluids and epinephrine, glucagon should be used. 1 milligram IV every 5 minutes until hypotension resolves, followed by an infusion of 5 to 15 micrograms/min.

26. Disposition and Follow-Up In the largest study of allergic reactions treated in the ED, admission occurred in only 4% of cases All unstable patients with anaphylaxis refractory to treatment or where airway interventions were required should be admitted to the intensive care unit. Patients who receive epinephrine should be observed in the ED, but the duration of observation is based on experience rather than clear evidence.

27. Disposition and Follow-Up If patients remain symptom free after appropriate treatment following 4 hours of observation, the patient can be safely discharged home. prolonged observation periods should be considered in patients with a past history of severe reaction and those using β-blockers. Other factors to consider in discharge planning include distance from medical care, whether the patient lives alone, significant comorbidity (including but not limited to asthma), and age

28. Outpatient Care and Prevention The patient should be instructed on how to avoid future exposure to the causative agent if known and possible. Patients can be discharged from the ED with an epinephrine autoinjector

29. Outpatient Care and Prevention Discharge Planning for Patients with Anaphylaxis Education Identification of inciting allergen, if possible Instructions on avoiding future exposure Instructions on use of medications and epinephrine autoinjector Advise about personal identification/allergy alert tag Medications Diphenhydramine, 25–50 milligrams PO for several days Prednisone, 40–60 milligrams PO for several days Epinephrine autoinjector for future reactions Referral to allergist

30. Outpatient Care and Prevention The patient should be instructed on how to avoid future exposure to the causative agent if known and possible. Patients can be discharged from the ED with an epinephrine autoinjector

31. Outpatient Care and Prevention Patients with anaphylactic reactions should be offered educational options [e.g., Web sites (see useful Web links summary on the DVD)], advice on advocacy groups, and education regarding food contamination for food allergies, and encouraged to wear personal identification of this condition (e.g., MedicAlert ® bracelets). β-blocker should be changed.

32. Outpatient Care and Prevention Treatment in the outpatient setting: antihistamines A short course of corticosteroids. All patients should be provided with a patient information sheet detailing signs and symptoms to watch for and clear instructions for follow-up and immediate return if there is any recurrence of symptoms. A written action plan on steps to take in the event of future allergen exposure or symptom development may reduce the severity of future attacks.