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Anaphylaxis

Anaphylaxis. Jesse Sturm, MD PEM Fellow October 3, 2007. This is a Test It is ONLY a Test. A 16 y/o girl just passed out after receiving her penicillin shot for strep throat (“doesn’t swallow pills”). Which of the following will be most useful to know in treating her:

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Anaphylaxis

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  1. Anaphylaxis Jesse Sturm, MD PEM Fellow October 3, 2007

  2. This is a Test It is ONLY a Test

  3. A 16 y/o girl just passed out after receiving her penicillin shot for strep throat (“doesn’t swallow pills”). Which of the following will be most useful to know in treating her: A Her Blood Pressure B Her Glucose level C Her Heart Rate D Your Heart Rate

  4. Which of the following is the safest and most efficient route to administer epinephrine in an allergy emergency: A IV B Sub Q C IM D PR

  5. When advising parents/patients on how to administer an “epi-pen” you should tell them to: A. hold it against the triceps and squeeze the trigger B. “stab” it into the anterior thigh C. hold it against the lateral thigh and push

  6. Which is NOT a clinical presentation of anaphylaxis: A. Vomiting and Diarrhea B. Syncope C. Altered Mental Status D. Itchy Tongue

  7. In counseling a 50kg 15 year old after a severe episode of anaphylaxis to a bee sting your best advice is that if they get stung again they first should take A. (2) 25mg diphenhydramine capsules PO B. (5) tsp diphenhydramine elixir PO C. .5mg epinephrine SQ D. 60mg prednisone PO

  8. Which of the following treatments has been shown to decrease the incidence of biphasic reactions: A. Corticosteroids B. Epinephrine C. Diphenhydramine D. Ranitidine

  9. Objectives • Definition of anaphylaxis • Epidemiology • Presenting signs and symptoms • What is the management algorithm • Supporting evidence for medication usage • Biphasic reactions

  10. History • First recorded case in Egyptian hieroglyphics 2641 B.C. – Pharaoh Menes died after wasp sting • Modern times – named by French scientists investigating anemone stings on dogs • “aphylaxis” • a – contrary • phylaxis – protection • Changed to anaphylaxis because sounded better

  11. Definition • Anaphylactic: allergic, IgE-mediated, immediate hypersensitivity reactions to protein substances • Requires previous exposure to antigen to form IgE • Anaphylactoid: clinically indistinguishable, NOT IgE-mediated i.e. contrast media • Does not require previous antigen exposure • Unknown mechanism • Anaphylaxis: clinical syndrome, regardless of mechanism

  12. Mechanism • IgE antibodies form upon initial Ag exposure • IgE binds to high-affinity Fc receptor on mast cell • Re-exposure, Ag bridges IgE → mast cell degranulation → release of preformed mediators (histamine, prostaglandin D2, leukotrienes) • Direct complement cascade activation by Ag resulting in anaphylatoxins C3a and C5a • Directly degranulate mast cells • Non-IgE and non-complement mechanism • Direct activity on mast cells • Hyperosmolar solutions (mannitol, radiocontrast)

  13. Epidemiology • Incidence varies – lack of consensus definition • ~ 10.5 per 100,000 person-years • 1% of all ED visits in both children and adults • Fatality rate: ~ 1% • 1500 deaths per year in all ages • 1300 drug induced • 100 food and sting induced • Children with atopy and asthma at higher risk • One study – males < 15yo, OR 1.9 for anaphylaxis compared to girls

  14. Clinical Criteria Anaphylaxis is highly likely when any one of the following 3 criteria are met. 1. Acute onset of an illness with involvement of skin, mucosal tissue, or both and at least one of the following: a. Respiratory compromise b. Reduced BP or end-organ dysfunction. • Two or more of the following that occur rapidly after exposure to a likely allergen for that patient: a. Involvement of the skin mucosal tissue b. Respiratory compromise c. Reduced BP or associated symptoms d. Persistent GI symptoms • Reduced BP after exposure to known allergen for that patient. Sampson et al Annals of Emerg Med Apr 2006

  15. Anaphylaxis TriggersReaction to previously known antigen: 21.1% • FOOD: 56% -Peanut, egg, dairy, seafood, food additives/dyes • DRUGS: 5% -Penicillins, cephalosporins, NSAIDs, other • INSECTS: 5% -Bees, wasps, ants • NO cause identified: 18% Braganza et al. Arch Dis Child 2006 N=57 Others: Blood products, Immunotherapy, Latex, Vaccines, Radiocontrast media

  16. Causes of Anaphylaxis: All Ages • Retrospective review • 601 patients with anaphylaxis • Excluded hymenoptera stings • Causes: Idiopathic: 59% Food: 22% Meds: 11% Exercise: 5% – rare in children Latex: 1% Webb M. Ann Allergy Asthma Immunol. 2006

  17. Foods • Peanut and Tree nuts: 1% Americans (3 million) allergic • Legumes: 25-35% also allergic to tree nuts • Shellfish • Fish • Milk • Eggs • Food additives: sulfites

  18. Arachis oil (peanut oil) Baked Goods and mixes Biscuits, cookies, pastries Candy Cereals Chocolate Emulsifiers, flavorings Ethnic foods: African, Chinese, Mexican, Thai, Vietnamese Ice Cream Margarine Milk formula Satay Sauce (thai sauce) Soft drinks Soups Sunflower seeds Vegetable fats and oils Foods That May Contain Peanut Oil

  19. Medication Triggers: All Ages • 69 anaphylactic events • Causes: Aspirin: 35% NSAID: 22% B-Lactam: 20% Insulin: 10% Protamine: 3% • PCN and cephalosporins cross react in 4-10% • Penicillin and NSAIDs most common in children • PCN IgE mediated 1:40,000 in children

  20. Venoms/Antivenins • 5 major stinging insects in the US: • honeybees • wasps • yellow jackets • hornets • fire ants

  21. Latex • Incidence low, except for risk groups: • Medically complex, multiple procedures • >1000 episodes and 15 deaths attributed • Surgical and dental procedures highest risk • RAST testing available

  22. Vaccinations • Rare event < 1.5 events per million • Most common MMR and Influenza • Both chick-derived cellular vaccines • MMR safe to give in egg allergy • Influenza contraindicated in egg allergy

  23. Anaphylaxis: Signs and Symptoms • Cutaneous 90% Urticaria and angioedema 90% Flushing 50% Pruritus without rash 5% • Respiratory 60% Throat pruritis/tingling 50% Dyspnea, wheeze 50% Upper airway angioedema 60% Rhinitis 20% • Dizziness, syncope, hypotension 35% • Abdominal 30% Nausea, vomiting, diarrhea, cramping pain Lieberman et al. American Academy of Allergy, Asthma and Immunology 2005

  24. Other Symptoms to Look For • Sense of impending doom • Uterine cramps • Visual disturbances • Metallic taste • Increased lacrimation • Seizure

  25. Anaphylaxis Boy

  26. Timing and Route of Exposure • Most symptoms occur within 5-30 minutes • Parentally injected medication and hymenoptera envenomation –more rapid • Oral ingestion – may be rapid or delayed • Food ingestions more often associated with GI symptoms

  27. Differential Diagnosis • Vasovagal reaction • Hereditary angioedema • Panic Attack • Urticarial disorders • Seizure • Vocal cord dysfunction • Systemic mastocytosis • Status asthmaticus, croup, tracheitis • Upper airway obstruction, foreign body

  28. Medications: Epinephrine H1 and H2 antagonists Vasopressors Glucagon Corticosteroids Albuterol Supportive measures: Oxygen Positioning Fluid Resuscitation Observation period Outpatient follow-up Management of Anaphylaxis

  29. Immediate Assessment • CR Monitor, pulseox • Supine positioning with Trendelenberg if shock • Assessment of ABC’s • Oxygen by NRB, wean as tolerated • Early elective intubation for significant hoarseness and/or lingual or oropharyngeal edema • Consider sedated intubation without paralysis

  30. Epinephrine • α1: promote vasoconstriction and decrease edema • β1: increase inotropy and chronotropy • Β2: bronchodilation and decreased mast cell degranulation • Dose: 0.01mg/kg: 0.1-0.5mg (0.5mL) of Epi 1:1000 • IM anterolateral thigh superior to SQ • Repeat dose at 5-10min intervals as needed • Persistent hypotension may reflect volume depletion and not failure of Epinephrine

  31. IM vs. SQ2 studies by Simons et alPatients NOT experiencing anaphylaxis • Single blind study in children, n=17 • MMEC= mean max epi concentration • Location of injections not described SQ: n=9. MMEC=1802pg/ml, @ 34min IM: n=8. MMEC=2136pg/ml, @ 8min Simons F. J Allergy Clin Immunol 1998 Simons F. J Allergy Clin Immunol 2001

  32. Serum Levels: Adults

  33. IM vs SQ: Adults • Adults:6 way crossover study, n=13 SQ deltoid: 2,877 pg/ml IM deltoid: 1,821 pg/ml Epipen thigh: 12,222 pg/ml IM thigh: 9,722 pg/ml Saline IM: 1458 pg/ml Saline SQ: 1495 pg/ml

  34. Epipen

  35. IV Epinephrine • Indicated for persistent hypotension after IM Epi, IVF, and positioning OR shock • IV/IO: Epi 1:10,000 at 0.01mg/kg (0.1mL/kg), max 1mg • Continuous infusion may be needed: 0.1-1μg/kg/min • Evidence based on a few adult studies • Can cause lethal arrhythmias • Requires careful continuous monitoring, especially in the elderly

  36. Epinephrine: Other Routes • Sublingual epinephrine vs. IM • Current study in rabbit model shows SL may be similar in efficacy • Not definitive • Inhaled Epi from MDI-type system shown to be ineffective

  37. Vasopressors • First line: intravenous epinephrine • Second line: Vasopressin 2 adult case reports of anaphylaxis with shock -42y/o s/p hornet sting, no improvement with 1mg Epi IV, improved with vasopressin (10 IU) -47y/o s/p wasp sting improved with vasopressin (40 IU) • Other vasopressors: dopamine or norepinephrine • Glucagon in persistently hypotensive pt taking beta-blockers Kill C, Int Arch Allergy Immunol, 2004.

  38. Glucagon • Theoretical utility and case reports of efficacy: • Activates adenylate cyclase independent of Beta receptor • May reverse refractory hypotension and bronchospasm • Particularly helpful if taking beta-blocker • Adults: 1-5 mg IV • Children 20-30 mcg/kg (max 1mg) • Followed by infusion 5-15mcg/min • Significant SE of emesis Javeed N. Cath & Card Diag, 1996.

  39. Anti-histaminesFor symptomatic treatment of urticaria-angioedema and pruritus • H1 antagonists (Diphenhydramine): • 25-50mg for adults • 1mg/kg for children (max 50mg) • IV route preferred for significant reactions • With H2 antagonists (Ranitidine, Cimetidine): -Double blind controlled trial demonstrated efficacy • Claritin and other second generation antihistamines may have more efficacy than diphenhydramine but lack IV formulation Lin R, Ann Emerg Med 2000.

  40. Primary Outcomes at 2 hours Anaphylaxis symptoms at 2 hours with and without Zantac Lin R, Ann Emerg Med 2000.

  41. Corticosteroids • No placebo-controlled trials supporting efficacy • Theoretical utility • May reduce late phase reaction based on results with asthma • Some studies have found them to be ineffective • Dosage: • methylprednisolone 1-2mg/kg IV Q6 up to 125mg • prednisone 1-2mg/kg (max=50mg) • No data on dexamethasone • Duration for 72hrs for latent reactions Biphasic reactions will be discussed in a few slides….

  42. Supportive Measures • Supplemental oxygen • Inhaled β2 agonists for wheezing • No data on inhaled Atrovent in anaphylaxis • Positioning in recumbent position • Fluid resuscitation • Vasodilatation and extravasation cause distributive shock • Circulating volume can drop 35% within 10min • May require multiple boluses of crystalloid and/or colloid (up to 60-80 mL/kg) Pumphrey R. J Allergy Clin Immunol 2003 Boulain T. Chest 2002

  43. Biphasic Reactions • Delayed reactions – up to 72 hours • Largest review in children - 6% incidence • Asymptomatic intervals 1.3 hrs to 28.4 hrs • Failure to administer prompt adequate doses of Epi increases risk of biphasic reaction • Route, quantity, and type of antigen NOT correlated with latent reaction • Symptoms and severity during initial reaction NOT predictive of latent reaction

  44. Observation PeriodCan we predict biphasic reactions?

  45. Predictors of biphasic reactions? • Delayed administration of epinephrine • Suspected but not proven • Patient requiring high doses of epinephrine • Lower doses of corticosteroids given • Ingested antigen There are NO reliable clinical predictors of biphasic reactions • Observation period individualized, but at least 6 hours

  46. Laryngoscopy? • Consider early elective intubation in severe cases • Endotracheal intubation for all children with orofacial bee stings AND any airway compromise • Not all facial swelling requires intubation Ditto A. Ann of All, Asthma and Immunol, 1995. Tome R. Am J of Otolaryng, 2005.

  47. Laboratory tests • Useful in uncertain cases • Prick skin tests: best screening test • high false positives; very few false negatives • may require food challenge • RAST: measures specific IgE • less sensitive than skin prick • Plasma Histamine: increases in 5-10 min, elevated for only 30-60min – not clinically useful • Serum Tryptase: peak 1-1.5 hrs, inc for up to 5hrs • Alpha: secreted constitutively • Beta: released during degranulation, ratio helpful • C1 inhibitor assay in hereditary angioedema • These tests have only limited utility in setting of acute severe anaphylaxis LaRoche D. Anethesiology 1991.

  48. Disposition(after appropriate observation period) • Severe reactions require observation for minimum 6-24hrs • Observation time based on: severity of initial reaction, home supervision, reliability of parent, access to care • High risk patients: • History of biphasic reaction, asthma, possibility of continued Ag absorption • Prescriptions for steroids and antihistamines for 72 hours Three key components of disposition: • Self-injectable epi-pen • Education about avoidance of triggers and return of symptoms • Follow-up evaluation with allergist

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