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Gavin Burgess EM Rounds 22 November 2007. Thanks Dr T Vander Leek. Phil. Anna. Axis. Introduction. “Anaphylaxis” coined in 1902 (Portier + Richet) Experimented with dogs and sea anemone venom immunisations Dogs unexpectedly died after previously tolerated doses
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Gavin Burgess EM Rounds 22 November 2007 Thanks Dr T Vander Leek
Phil Anna Axis
Introduction • “Anaphylaxis” coined in 1902 (Portier + Richet) • Experimented with dogs and sea anemone venom immunisations • Dogs unexpectedly died after previously tolerated doses • Lieberman in Allergy: Principles and Practice v.5, 1079-92
Definition • A Severe, potentially fatal, systemic allergic reaction that occurs suddenly after contact with an allergy-causing substance • Sampson et al JACI 2006;117:391-7
Definition • A severe allergic reaction to any stimulus, having sudden onset, involving one or more body systems with multiple symptoms • Canadian Anaphylaxis Guidelines www.allergysafecommunities.ca
Definition • An acute, life-threatening reaction mediated by IgE • IgE-mediated Type I hypersensitivity • Release of Mast cell and Basophil contents
Biochemical Mediators and Chemotactic Substances • Degranulation of mast cells and basophils. • Preformed granule-associated substances, e.g., histamine, tryptase, chymase, heparin, histamine-releasing factor, other cytokines. • Newly generated lipid-derived mediators, e.g., prostaglandin D2, leukotriene B4, PAF, LTC4, LTD4, and LTE4.
Biochemical Mediators and Chemotactic Substances • Eosinophils may play pro-inflammatory role (release of cytotoxic granule-associatedproteins) or anti-inflammatory role (e.g., metabolism of vasoactive mediators)
Incidence • Analysis of published studies of most common causes • 3.3 to 4 million Americans at risk. • 1,433 to 1,503 at risk for fatal reaction. Neugut, Ghatak, Miller Arch Int Med 2001
Incidence Based on Epinephrine Rx for Out-of-Hospital Use • From Canada and Wales. • 0.95% of population in Manitoba, Canada. • 0.2 per 1000 in Wales. • Incidence increased in Wales between 1994 & 1999. Simons, Peterson, BlackJACI 2002 Rangaraj, Tuthill, Burr, AlfahamJACI 2002
Case 1 • 6y at friend’s birthday party, ate peanut-containing peanuts • Tingling around mouth, thick tongue, lip swelling • In ED, urticaria, swollen lips and tongue, flushing • Vitals: P120, RR 35-40, afebrile, BP 70/40
Signs of anaphylaxis • Loss of consciousness • “sense of impending doom”
Signs of anaphylaxis • Cutaneous – urticaria, angioedema, pruritis, erythema/flushing • Oral – tingling lips/tongue/palate, swollen tongue/lips • Ocular – periocular oedema, erythema, conjunctival injection, tearing
Signs of anaphylaxis • Respiratory • Upper airway – voice change, throat clearing, airway obstruction (tongue, laryngeal or oropharyngeal oedema), sneezing, nasal pruritis, rhinorrhea, congestion • Lower airway - wheeze, cough, tight chest
Signs of anaphylaxis • Gastrointestinal – nausea, vomiting, cramps, diarrhea, urgency, incontinence • Genitourinary – uterine cramps, urgency, incontinence • Cardiovascular – hypotension, arrhythmia, shock, syncope, chest pain
Signs of anaphylaxis Lieberman in Allergy: Principles and practice v.5 1079-92
Case 2 • 25y F, known ED, stands, has syncopal event, diaphoresis, nausea • Looks pale, P110, BP (L) 110/70, BP (s) 90/50, RR18
Differential Diagnosis • Anything can resemble anaphylaxis • Vasovagal, globus hystericus, status asthmaticus, hereditary angioedema, hypoglycaemia, FB aspiration, seizures, etc.
Hypersensitivity • Type I – immediate, preformed • Almost all <60min • Can skin test, IgE-mediated ONLY • Type II – cytotoxic, IgM, IgG on cell surface • <72hours
Hypersensitivity • Type III – immune complex, serum sickness, IgG • 1-3 week delay LN, arthritis • Type IV – T-cell mediated, NO antibodies • >48 hours
Adverse Reactions • Mixed reactions • Erythema multiforme -> Stevens-Johnson, fixed drug reaction • Unpredictable, non immune mediated “pseudo allergic” • Red man, morphine, ACEI, G6PD • Predictable reactions
Food Vaccines Medications Blood products Latex Drugs and biologicals Exercise Insect venom Idiopathic Causes
Significance • Food allergy is now the most common cause of anaphylaxis in the ED. • >1/3 of presentations • Sampson HA. Pediatrics 2003;111:1601-8
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Risk Factors • Injected material vs ingested material • Atopy • Asthma (even if well controlled) • Failure to identify proper trigger • Previous reactions to trigger • Less risk at extremes of age
Prev anaphylaxis Asthma Failure to identify trigger Teens Β-blockers/ ACEI Failure to administer epinephrine immediately Risk Factors for severe anaphylaxis
Case 1 cont. • Symptoms worsening. Wheezing, lethargic. • Sats 89%, prolonged expiration phase, Little air movement on auscultation • Management?
Management • Failure to administer epinephrine early is the single most important risk factor for fatal or near fatal reactions • Bock, SA J. Allergy Clin Immunol 2001;107:191-3
Management I. Immediate Intervention a)Assessment of airway, breathing, circulation, and mentation. b) Administer EPI, 1:1000 dilution, 0.3 - 0.5 ml (0.01 mg/kg in children, max 0.3 mg dosage) IM, to control SX and BP. Repeat, as necessary. Kemp and Lockey JACI 2002 Simons et al JACI 1998 Simons, Gu, Simons JACI 2001
Management c) IM into the anterolateral thigh produces higher & more rapid peak plasma level versus SQ & IM in arm. With moderate, severe, or progressive ANA, EPI IM into anterolateral thigh. Alternatively, an EPI autoinjector given through clothing in same manner. Repeat, as necessary
Epinephrine route of administration Simons JACI 1998;101:33-7
Management d) Aqueous EPI 1:1000, 0.1- 0.3ml in 10ml NS (1:100,000 to 1:33,000 dilution), IV over several minutes prn. e) For potentially moribund subjects, tubercular syringe, EPI 1:1000, 0.1 ml, insert into vein (IV), aspirate 0.9 ml of blood (1:10,000 dilution). Give as necessary for response
Management II. General measures a) Place in recumbent position and elevate lower extremities. Up to 35% of intravascular fluid may be lost in 10 min! Pressors may fail to work b) Maintain airway (endotracheal tube or cricothyrotomy).
Management c) O2, 6 - 8 liters/minute. d) NS, IV. If severe hypotension, give volume expanders (colloid solution) – 35% of blood volume can be lost in 20 min. e) Venous tourniquet above reaction site. ? if decreases absorption of allergen.
Management III. Specific Measures that Depend on Clinical Scenario a) Aqueous EPI 1:1,000, ½ dose (0.1- 0.2 mg) at reaction site.
Management b) Diphenhydramine, 50 mg or more in divided doses orally or IV, maximum daily dose 200 mg (5 mg/kg) for children and 400 mg for adults. c) Ranitidine, 50 mg in adults and 12.5 - 50 mg (1 mg/kg) in children, dilute in D5W, total 20 ml, inject IV, over 5 minutes. (Cimetidine 4 mg/kg OK for adults, not established for pediatrics).
Management d) Bronchospasm, nebulized salbutamol e) Aminophylline, 5mg/kg over 30 min IV may be helpful. Adjust dose based on age, medications, disease, current use. f) Refractory hypotension, give dopamine, 400 mg in 500 ml G/W IV 2 - 20 μg/kg/min more or less.
Management g) Glucagon, 1- 5 mg (20 - 30 μg/kg [max 1 mg] in children), administered IV over 5 minutes followed with IV infusion 5-15 μg/min. h) Methylprednisolone, 1- 2 mg/kg per 24 hr; prevents prolonged reactions and relapses- no studies, though i) Cetirizine
Management • Biphasic response in some individuals, unpredictable • Recommended observation for 4h
Epipens • 0.15mg or 0.3mg doses available • Adult 0.3mg • Paeds • 0.15mg (10-25kg) • 0.3mg (>25kg)
Epipens Simons JACI 2000;105:1025-30
Case 3 • 70y obese hypertensive, started on ACEI (captopril). • Prev. ETT, thyroid surgery • To ED with swollen face and lips. No largyneal involvement