History of anaphylaxis Anaphylaxis William Reisacher, MD FACS FAAOA Assistant Professor Department of Otorhinolaryngology Weill Cornell Medical College 2640 BC: Menes, an Egyptian pharaoh, was depicted in hieroglyphics dying from the sting of a wasp. 1902: Portier and Richet introduce the term anaphylaxis. 1933: Rubber gloves are first recognized as an allergen. Epidemiology Responsible for approximately 1000 deaths per year in the U.S. 1 in every 3000 patients in U.S. hospitals suffers an anaphylactic reaction. Overall risk of death from anaphylaxis is 1%. 75% from airway edema 25% from hypotension Definition Immediate immunologic reaction characterized by the contraction of smooth muscle and dilation of capillaries due to the systemic release of pharmacologically active substances. Pathophysiology Type I Hypersensitivity Immediate release of histamine, chymase, tryptase, heparin, chondroitin sulfate from mast cells Late phase (4-6 hours) leads to release of prostaglandins, leukotrienes and platelet activating factor. 1
Classification of anaphylaxis Allergen-induced anaphylaxis: Antigens bind to IgE receptors or complement (C3a, C5a), causing degranulation of mast cells. Non-allergen-induced anaphylaxis: Direct activation of mast cells independent of IgE or the complement cascade (Anaphylactoid) Causes of anaphylaxis Foods (33%) Idiopathic (19%) Insect stings (14%) Other (14%) Medications (13%) Exercise (7%) Causes - Foods Peanuts Tree nuts Shellfish Milk Eggs Bisulfite additives to foods Causes Insect stings Hymenoptera order honey bees, hornets, wasps, yellow-jackets and fire ants. Anaphylactic reactions occur in about 0.5% to 3% of the U.S. population Without immunotherapy, risk of repeat reaction is 60%. With immunotherapy, risk is 3%. Causes - Other Blood products Latex Iatrogenic allergy testing, immunotherapy. Causes - Medications Beta-lactam antibiotics responsible for 75% of fatal drug reactions in the U.S. NSAIDS Opioid analgesics ASA 2
Causes - Exercise More common after vigorous, anaerobic activity Foods possibly acting as a cofactor Wheat and shellfish most commonly implicated. Anaphylactoid reactions Drugs morphine, codeine, vancomycin Hyperosmolar agents radiology contrast material Histamine in foods strawberries, tomatoes Saurine in spoiled fish Exercise Mastocytosis Incidence of Anaphylaxis 1999 Hurst et al. conducted a multi-center study of 27 otolaryngic allergy practices over one year. 1,144,000 injections Major systemic reactions occurred in 0.005% of shots (approximately 57) 87% of reactions occurred within 20 minutes of the injection 46% of patients had history of asthma Incidence is 0.02% among general allergists Diagnosis of anaphylaxis Vasodilation warm, red skin with rapid pulse and low BP Itching/urticaria Coughing/wheezing secondary to smooth muscle contraction and increased mucus secretion and airway edema. GI symptoms, nasal symptoms, headache, chest pain or feeling of doom. Skin Rash During Anaphylaxis Differential diagnosis Asthma Angioedema (C1 esterase inhibitor deficiency or ACE inhibitors) Flushing syndromes pheochromocytoma, carcinoid Coronary event Pulmonary embolus Vasovagal reaction Hypoglycemia Seizure Hysteria 3
Vasovagal Reaction The Faint Slow pulse Normal BP generally maintained Pale skin Cool and clammy No coughing or wheezing No itching or urticaria Immediate LOC May exhibit brief seizure activity Ammonia ampules may be used Treatment is cool compresses, time and recumbency Anaphylaxis Risk Factors: Testing Uncontrolled asthma Current URI In season for major allergen Patient with multiple high sensitivities Recent large exposure to allergen Patients on beta-blockers Anaphylaxis Risk Factors: Treatment First few weeks of immunotherapy First injection from a new vial Dose escalation while levels of a seasonal allergen are high Increasing size of local reactions Doses approaching maintenance Anaphylaxis Risk Factors: Beta-blockers Beta receptors are located on most cells Beta-1: primarily in the heart increases rate and contractility Beta-2: primarily in smooth muscle which causes relaxation Two type of beta-blockers Non-selective: labetalol, nadolol, propranolol, timolol Beta-1 selective: atenolol, metoprolol At high doses, all become non-selective Anaphylaxis Risk Factors: Beta-blockers Beta-blockers are contraindicated in severe asthma and COPD. Essential uses of beta blockade Improves post-mi survival Required for certain arrhythmias Hypertrophic subaortic stenosis (IHSS) Intermediate uses of beta blockade Glaucoma Essential tremor Angina Pre-op use for pheochromocytoma or hyperthyroidism Non-essential uses of beta blockade HTN Migraine HA Anaphylaxis Risk Factors: Beta-blockers Beta-blockers are pro-allergenic Decreased stability of mast cells and enhanced mediator release Increased bronchospasm Beta-blockers make treatment of anaphylaxis more difficult Cases are more severe Epinephrine not as effective at usual dose Increased dose of epinephrine may lead to unopposed alpha effect -> HTN, MI or CVA 4
Avoidance of Anaphylaxis Select appropriate initial doses for testing Avoid testing with cross-reacting antigens Administer testing and treatment only when patient is in good health No vigorous exercise before or after testing/treatment Mix antigens and prepare vials in a quiet area Have someone else check your math Perform vial testing before the first dose Gradual dose escalation Double-check patient s name and dose prior to the injection 20 minute post-injection observation with arm check Educate patients about recognizing signs of a severe reaction and the importance of carrying auto-injectable epinephrine Preparation is the Key! CPR certification for relevant staff Education of staff about signs and symptoms of anaphylaxis Conduct regular drills Keep medications and supplies readily available and current. Preparing the Office Treatment area with chair/bed Ammonia ampules BP cuff and Stethoscope Oxygen / mask / ambu bag Suction devices Intubation laryngoscopes and ET tubes IV setup (pole, IV fluid, extension sets, tape, angiocaths) Needles and syringes Medications with dosing/mixing sheets Consider purchasing an office AED Treatment Outline Call for help (office staff and/or 911) and have staff member bring supplies if not in immediate area. Place patient in supine position and loosen clothing. ABC assessment, obtain vitals If patient comfortable and vitals stable, consider antihistamine, otherwise administer EpiPen Apply tourniquet above injection site or place ice on the injection site Administer oxygen and secure airway if necessary Establish intravenous line and start rapid infusion Repeat vitals and administer medications as needed. Medications: Epinephrine Alpha & beta agonist Adult 0.3-0.5 cc (1:1000) IM or SC Children 0.01 mg/kg (1:1000) IM or SC EpiPen (0.3mg) EpiPenJr (0.15mg) cutoff is about 60 lbs. May need to repeat in 10-15 minutes Decrease dose 10% for TCA, MAO Medications: Antihistamines H1 antagonist Give non-sedating antihistamine orally after epinephrine Diphenhydramine 1 mg/kg IV or IM Always give H1 blocker before H2 H2 antagonist Ranitidine 50 mg slow IVP Cimetidine 300 mg slow IVP 5
Medications: Steroids Necessary if patient is asthmatic Beneficial from late phase reactions Prednisone 40 mg PO Hydrocortisone 250-500 mg IV/IM Dexamethasone 20 mg IV Medications: Bronchodilators Albuterol (fast acting bronchodilator) May use up to 20 puffs to break bronchospasm or overcome beta blockade Use early, first signs of respiratory distress Ipratropium bromide (Atrovent) Anticholinergic not affected by beta-blockade Use 2 or more puffs (all ages) Magnesium sulfate 1 gram in 50cc NS, slow IVP over 5 minutes Good for patients under beta-blockade Medications: Dopamine Use if unable to maintain BP with fluids Start with 1 µg/kg/min IV Add 400 mg ampule to 250cc D5W/NS Begin drip at about 0.05 ml/min Titrate up to 20 µg/kg/min IV Below 10 µg/kg/min, it is primarily a betaagonist Decrease dose 10% if on MAO inhibitors Medications: Other Heparin Binds histamine and releases histaminases 100 USP Units/Kg IV (all ages) Nitroglycerin 0.4mg SL for angina Phentolamine (pure alpha-blocker) Use for hypertensive crisis, stop pressors first 5-10mg (adults) / 1mg (children) IV q 5-15 min Lidocaine ventricular ectopy Atropine - bradyarrhythmias Anaphylaxis Follow-up Once the patient is stabilized, EMS should transfer to the hospital. Observe for late phase reactions Continue steroids and antihistamines for 24-48 hours. 6