Anaphylaxis Will Davies May 2014
Anaphylaxis Algorithm EMCore 2014 History suggestive of anaphylactic reaction? Acute onset of illness associated with trigger Relative bradycardia with hypotension without trigger Previous evidence of allergy or anaphylaxis Signs of life threatening anaphylaxis: Airway: Swelling, voice changes, stridor Breathing: Tachypnoea, wheeze, cyanosis, sats<92% on air, confusion Circulation: Pallor, clamminess, hypotension, drowsiness Call for help Remove allergic stimulus (if identified) ADRENALINE I.M. Raised patient s legs in supine position Airway: Early intubation should be considered Breathing: High flow O2 by mask Circulation: Large I.V. access and fluid bolus, 20ml/kg over 2 mins Continuous non-invasive monitoring Resolves Inadequate response Observe for a minimum of 4 hrs after the resolution of all symptoms and signs Take blood for serum mast cell tryptase on arrival, 1 h after arrival and prior to discharge Admit longer (overnight) those with severe reactions, a history of life-threatening reactions or poorly controlled asthma, and those who present late in the evening Outpatient follow up by a specialist allergist is recommended for all those with moderate severe reactions Arrange for an EpiPen, demonstrate correct use with an EpiPen Trainer and provide a written action plan (http://www.allergy. org.au) if there is a significant risk of re-exposure and outpatient follow up will be delayed Upper Airway Obstruction Nebulized adrenaline (5 mg in 5 ml, i.e. 5 ml of 1:1000) may provide some relief Prepare for surgical airway Start an i.v. adrenaline infusion as per hospital guidelines/ protocol OR Repeat i.m. adrenaline every 3 5 min as needed Hypotension Bronchospasm Continuous salbutamol nebulizers or continuous actuations of metered dose inhaler into ventilation circuit if intubated) I.V. hydrocortisone 5mg/kg 6 hourly followed by oral prednisone 1 mg/kg (max. 50 mg) for 4 days Repeat normal saline boluses 10 20mL/kg as needed, up to 50 ml/kg total over the first 30 min I.V. atropine 0.02 mg/kg if severe bradycardia (minimum dose 0.1 mg). I.V.vasopressors to overcome vasodilation (vasopressin 10 40 units in adults, or metaraminol 2 10 mg in adults). For anaphylactic cardiac arrest, rapid escalation to high dose adrenaline (3 5 mg every 2 3 min) might be effective I.V.glucagon/phosphodiesterase inhibitors/balloon pump if β-blocked or heart failure: Glucagon dose in adults: load with 1 5 mg over 5 min, followed by 5 15 μg/min
Definition and Diagnosis A serious allergic or hypersensitivity reaction that is rapid in onset and may cause death. Diagnostic criteria are based on consensus and have never been comprehensively validated Often underdiagnosed: Does not always include the classic rash History may not be clear at presentation No definitive laboratory marker
Gell-Coombs Classification of Hypersensitivity Type of Reaction Time to Onset of Clinical Signs Mechanism Type I (anaphylactic) <30 mins IgE crosslinking on mast cells or basophils causes release of reactive substances. Type II (cytotoxic) 5-12 hours Antigen triggers production of IgM and IgG which for a membrane attack complex with complement and destroy the target cell. Type III (immune complex) Type IV (cell-mediated/ delayed type) 3-8 hours Antibodies and antigens combine triggering inflammation 24-48 hours Antigens trigger cytotoxic T cells to kill target cells. Examples Anaphylaxis Hayfever Atopic asthma Transfusion reactions Serum sickness Transplant rejection
Mechanism of Type I Hypersensitivity Reaction IgE-antigen reaction occurs on the surface of basophils and mast cells leads to receptor cross-linking and degranulation, of vasoactive amines (histamine and serotonin) and other agents (heparin, eosinophil and neutrophil chemotactic factors, platelet-activating factor, a variety of cytokines and prostaglandins and leukotrienes) from the cytoplasmic granules.
Other Interpretations: Infection Centric View of Immune Responses Pathogen Gell Coombs scheme Effector mechanism Possible untoward consequences Gastrointestinal or respiratory tract multicellular, metazoan parasites Type I Orchestrated by Th2 cells. Effectors include IgE antibody (þ IgE1 in mouse), mast cells, Paneth cells, mucosal glands, smooth muscle cells Anaphylaxis, hay fever, asthma Extracellular microorganisms (staphylococci, streptococci) Type II Antibodies to surface antigens of microorganisms, C5a release, chemotaxis of polymorphonuclear leukocytes (PMNs) to site of infection Certain drug reactions; the vasculitides such as polyarteritis nodosa; Graves disease (agonist antibody to thyroid stimulating); myasthenia gravis (antagonist antibody to acetylcholine receptor) Circulating viral particles, such as in viraemia Type III Antibodies complexing with and inactivating circulating viral particles; subsequent solubilization by C. Immune complex disease, such as in systemic lupus erythematosus (SLE) Viral or intracellular bacterial infection Type IV CD4 and CD8 cells recognizing MHC antigens presenting viral peptides Insulin dependent diabetes; Hashimoto s thyroiditis Extracellular, indigestible agents, such as Mycobacterium tuberculosis, Schistosome eggs Not included Formation of granulomas that encapsulate and isolate the pathogen. Driven by innate immunity ( foreign body ) or type 1 (M. tuberculosis infections) or type 2 (Schistosome eggs) cytokines Sarcoidosis? The Gell Coombs classification of hypersensitivity reactions: a re-interpretation. Rajan TV. TRENDS in Immunology Vol.24 No.7 July 2003
Diagnostic Criteria Anaphylaxis is Likely if One of the Following are Present: 1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both and at least one of the following: A. Respiratory compromise (eg, dyspnoea, bronchospasm, stridor) B. Reduced BP or associated symptoms of shock 2. Two or more of the following occurring rapidly after exposure to a likely allergen for that patient (minutes to several hours): A. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula) B. Respiratory compromise (eg, dyspnoea, wheeze-bronchospasm, stridor, hypoxaemia) C. Reduced BP or associated symptoms (eg, hypotonia, collapse, syncope, incontinence) D. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 3. Rapid onset of reduced BP after exposure to a known allergen for that patient: A. Adults: systolic BP of less than 90 mmhg or more than 30 percent decrease from normal baseline B. Infants and children: low systolic BP or greater than 30 percent decrease in systolic BP Sampson HA 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. J Allergy Clin Immunol 2006; 117:391
Symptom Frequency Skin symptoms and signs: 90 % of episodes; generalized hives, itching or flushing, swollen lips-tongueuvula, periorbital oedema, conjunctival swelling. Respiratory symptoms and signs: 70 % of episodes; nasal congestion, hoarse voice, sensation of throat closure or choking, stridor, shortness of breath, wheeze, cough. Gastrointestinal symptoms and signs: 45 % of episodes; nausea, vomiting, diarrhoea, and cramping abdominal pain. Cardiovascular symptoms and signs: 45 % of episodes; hypotonia (collapse), syncope, incontinence, dizziness, tachycardia, and hypotension
Severity Categorisation Grade of anaphylaxis * Mild Skin and subcutaneous tissues only Moderate Respiratory, cardiovascular or gastrointestinal involvement Severe Hypoxia, hypotension or neurological compromise Features Generalized erythema, urticaria, periorbital oedema or angioedema Dyspnoea, stridor, wheeze, nausea, vomiting, dizziness (presyncope), diaphoresis, chest or throat tightness, or abdominal pain Cyanosis or SpO2 92%, hypotension (SBP <90 mmhg in adults), confusion, collapse, LOC or incontinence * The mild grade does not represent anaphylaxis according to the National Institute of Allergy and Infectious Disease-Food Allergy and Anaphylaxis Network Adapted from: Brown SGA. Clinical features and severity grading of anaphylaxis. J. Allergy Clin. Immunol. 2004; 114: 371 6.
Laboratory Tests Test Total tryptase (serum/plasma) Mature tryptase (serum/plasma) Histamine (plasma) Histamine (24 hour urine) Comment Maximal elevation above baseline 15 to 60 minutes after onset of anaphylaxis; declines to baseline with a t 1/2 of ~2 hours. Only 70% sensitive but reasonable specificity if acute and baseline levels are compared.(1) Mature tryptase. Peaks 15 to 60 minutes after the onset of anaphylaxis and then declines with a t 1/2 of ~2 hours. Peaks 5 to 10 minutes after symptom onset and declines to baseline by 15 to 30 minutes. Histamine may be released ex vivo by vigorous phlebotomy. May be elevated in urine collected up to 24 hours after symptom onset, but histamine-containing foods and histamine-producing mucosal bacteria may be problematic. 1. Brown SG, Blackman KE, Heddle RJ. Can serum mast cell tryptase help diagnose anaphylaxis? Emerg. Med. Australas. 2004; 16: 120 4.
Anaphylaxis Triggers Common: Foods: most commonly peanuts, tree nuts, egg, seafood and fish, cow s milk, wheat Medications: most commonly antibiotics Insect stings (bees and wasps) Natural rubber latex Unidentified (no cause found; idiopathic anaphylaxis) Less common: Exercise Semen Food additives: monosodium glutamate, metabisulphite Hormonal changes: menstrual factors Topical medications Transfusions Kim and Fischer Allergy, Asthma & Clinical Immunology 2011 7(Suppl 1):S6
Anaphylaxis Triggers in Australia (Tasmania) Venomous stings and bites, n = 342 (30%) Ant (Myrmecia spp) 165 Bee (Apis mellifera) 71 Yellow jacket (Vespula germanica) 16 Others 11 Unidentified sting or bite 79 Iatrogenic, n = 250 (22%) Antibiotic 145 Nonsteroidal anti-inflammatory 32 Narcotic 11 Radiologic contrast 7 ACE inhibitor* 4 Vaccine 4 Others or uncertain 47 Food, n = 205 (18%) Sea food 47 Nut 46 Egg 14 Monosodium glutamate! 7 Kiwi fruit 4 * Does not include simple angioedema Brown SGA. Clinical features and severity grading of anaphylaxis. J. Allergy Clin. Immunol. 2004; 114: 371 6.
Ant (Myrmecia spp), Jack Jumper et. Al. Causes of ant sting anaphylaxis in Australia: the Australian Ant Venom Allergy Study. SGA Brown Et Al. Med J Aust 2011; 195 (2): 69-73 A. A large bulldog ant (Myrmecia pyriformis) and a smaller jumper ant and (inset) a green-head ant (~ 6mm long, dark black metallic green). B. JJA, usually 10 12mm long, black body with orange yellow mandibles, and moves with short jerks and jumps. C. Another jumper ant, Myrmecia nigrocincta, which is similar in size and behaviour to the JJA but with bright red body segment(s). D. A typical jumper ant nest, covered with small stones. E-H. Bulldog ants of the Myrmecia gulosa species group, 20 30mm long and a variety of colours.
Ant Distribution Causes of ant sting anaphylaxis in Australia: the Australian Ant Venom Allergy Study. SGA Brown Et Al. Med J Aust 2011; 195 (2): 69-73
Treatment of Anaphylaxis The cornerstones of management are the supine position, adrenaline and volume resuscitation. An intramuscular dose of adrenaline is recommended to initiate treatment. If additional adrenaline is required an intravenous infusion is efficacious and safer than intravenous bolus administration. Additional bronchodilator treatment with continuous salbutamol and corticosteroids are used for severe and/or refractory bronchospasm. Aggressive volume resuscitation, selective vasopressors, atropine (for bradycardia), inotropes that bypass the β-adrenoreceptor and bedside echocardiographic assessment should be considered for hypotension that is refractory to treatment.
Emergency Management of Anaphylaxis Extracted from: Anaphylaxis: Clinical concepts and research priorities. Simon GA Brown. Emergency Medicine Australasia (2006) 18, 155 169
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