Allergies, Anaphylaxis, Adrenaline, and Auto-injectors. Julie Brown, MDCM, MPH Vancouver, Sept 19 th, 2015

Transcription

1 Allergies, Anaphylaxis, Adrenaline, and Auto-injectors Julie Brown, MDCM, MPH Vancouver, Sept 19 th, 2015

2 Overview Case Epidemiology Pathophysiology Clinical Management Emergency Management After the reaction Auto-injectors Advocacy

3 Case A 2-year old healthy boy, no allergies 17:00 ate a pistachio nut 17:20 profuse rhinorrhea 17:30 vomits Emergency Department (ED): 17:50 vomits on arrival P 100 BP 90/60 R 24 T 37 Mild rash Mouth and lungs are normal Says his stomach hurts

4 Allergies 40 million people in the U.S. have an allergy 15 million have a food allergy 2 million have insect venom allergy

5 Allergies in Children 6 million children in the U.S. have food allergies = 8% of children = 1 in 13 children = 2 per classroom 30% with allergies have multiple allergies 3% have had a severe reaction to food Gupta 2011 Pedatrics 1,500 anaphylaxis deaths each year, 150 due to food Economic cost $25 billion a year 50% increase between 1997 and 2011

6 Why are Allergies Increasing? Unknown Many theories, controversial: Leaky gut is quite popular Best support is for the hygiene hypothesis Imbalance between T-helper1/T-helper2

7 Allergies -- Treatment Avoidance 15% of people with allergies have an allergic reaction each year. >50% react outside the home.

8 Allergies -- Treatment Immunotherapies Still under investigation, not widespread. Generally not a cure (desensitization not tolerance). Time intensive, takes cooperation from the child, expensive.

9 Anaphylaxis An acute systemic allergic reaction It is generally a Type I hypersensitivity Re-exposure to an antigen IgE mediated response Typically a common environmental protein that is not intrinsically harmful

10 Histamine Synthesized and stored in mast cell and basophil granules The primary mediator of the inflammatory response 4 receptors H1: endothelial cells (85%), smooth muscle H2: endothelial cells (15%), gastric parietal cells, cardiac muscle (myocardium & coronary arteries) H3: Central nervous system Modulates neurotransmission Decreases histamine release H4: mast cells, eosinophils, T cells, dendritic cells Regulates immune responses

11 Tissue Effects of Histamines Cardiovascular Decreased blood pressure Increased heart rate Edema (separation of endothelial cells & increased permeability) Respiratory Broncho-constriction Hyper-secretion from glandular tissue Gastrointestinal Smooth muscle contraction Skin Vascular leakage

12 How Kids Describe An Allergic Reaction to Food Food tastes like something is wrong with it Food is spicy, tongue is burning Bump or something poking tongue Tongue or mouth itches Hair in mouth or on tongue Lips/tongue/spit feels big Rocks/bone/frog/something stuck in throat Bugs in ears Eyes itching, burning or leaking Eyes going in and out and dark Sense of doom, something is wrong Tummy hurts, feel sick, ate a volcano, bugs in stomach Body feels heavy or stuffy or hot

13 Definition of Anaphylaxis for Emergency Health Professionals Working Definition: Anaphylaxis is a serious reaction that is rapid in onset and may cause death. It is usually due to an allergic reaction but can also be non-allergic. Nowak 2013 J Emerg Med

14 NIAID/FAAN (Sampson) Assessment Criteria There undoubtedly will be patients who present with symptoms not yet fulfilling the criteria of anaphylaxis yet in whom it would be appropriate to initiate therapy with epinephrine, such as a patient with a history of near-fatal anaphylaxis to peanut who ingested peanut and within minutes is experiencing urticaria and generalized flushing. Sampson HA, et al. J Allergy Clin Immunol. 2006;117:391-97

15 Emergency Department Anaphylaxis Guidelines Patients with anaphylaxis can present with symptoms not meeting the criteria for anaphylaxis and yet require administration of epinephrine. Delayed administration of epinephrine is associated with poor outcomes and mortality. Campbell RL, et al. Ann Allergy Asthma Immunol. 2014;

16 Time from Exposure to Symptoms 76 patients with food, sting or drug anaphylaxis: Onset <1 minute to 9.7 hours. Mean time was 31 +/- 71 minutes Median of 10 minutes. Most happen in the first hour after exposure Lee 2000 Pediatrics

17 Epinephrine mechanisms of action Stimulation of α adrenoceptors peripheral vascular resistance and thus blood pressure coronary perfusion peripheral vasodilation, angioedema, hives Stimulation of β 1 adrenoceptors has both positive inotropic (force) and chronotropic (rate) cardiac effects Stimulation of β 2 receptors results in: Smooth muscle relaxation bronchodilation Increased intracellular cyclic AMP production in mast cells and basophils, reducing release of inflammatory mediators

18 Epinephrine the wonder drug Effect of Cytokines Effects of Epinephrine Effects of Anti-histamines (H1 blockers) Stabilizes mast cells Vasodilation Vasoconstriction block histamine H1 receptor-mediated vasodilation Bronchoconstriction Bronchodilation block histamine H1 receptor-mediated bronchoconstriction Smooth muscle contraction Smooth muscle relaxation block histamine H1 receptor-mediated muscle contraction pulse pulse? (via vasoconstriction or anticholinergic effects) BP BP? (via vasoconstriction or anticholinergic effects) coronary perfusion coronary perfusion Onset of Action: Almost Immediate minutes for Benadryl

19 Epinephrine the wonder drug No absolute contraindications Most adverse events -- overdose or IV route. Nearly zero risk in children with right dose/right route Very low risk in adults with right dose/right route Higher risk populations: Elderly Hypertension History of stroke, heart attack, ischemic heart disease Unknown risk to fetus Benefits generally outweigh risks

20 Epinephrine a word about ischemia It should be stressed that adrenaline is not contraindicated in individuals with underlying ischemic heart disease, as the decrease in filling pressure due to anaphylaxis is likely to result in further coronary ischemia McLean-Tooke et al. BMJ 2003;327:

21 Epinephrine Side Effects Palpitations Tachycardia & arrhythmias Hypertension Headache Tremor, weakness Pallor, sweating Nausea/vomiting Nervousness/anxiety Angina/ischemia Stroke

22 Epinephrine Dosing Emergency Department/Hospital Dosing 1:1,000 concentration mg in adults 0.01 mg/kg to a max of 0.3 mg in children For example, 10 kg (22 lb) child 15 kg (33 lb) child 20 kg (44 lb) child 25 kg (55 lb) child 30 kg (66 lb) child 0.1 mg 0.15 mg 0.2 mg 0.25 mg 0.3 mg

23 Epinephrine Dosing Auto-injectors 0.15 mg if < 30 kg (66 pounds) 0.3 mg if >= 30 kg (66 pounds) Check and inject (EMS): 1:1,000 concentration 0.15 mg if < 30 kg (66 pounds) 0.3 mg if >= 30 kg (66 pounds) Repeat every 5 minutes as needed Can be sooner if clinically warranted (Lieberman 2010 AAAI)

24 Epinephrine Dosing Largely theoretical.? Extrapolated from resuscitation (1:10,000) epi? Small number of studies looking at serum epi levels in healthy adult males, after an injected dose, with variable results. One study looking at levels in healthy children with allergies. No studies of levels in patients in anaphylaxis. No studies comparing serum levels with clinical effect.

25 Emergency Management -- Epinephrine Epinephrine is the only first-line treatment for anaphylaxis. Withholding epinephrine in favor of antihistamine, steroid administration, and watchful waiting, or even establishing intravenous access in patients with a reasonable suspicion of anaphylaxis is risky even in the presence of mild presenting symptoms. Delaying administration of epinephrine has been associated with increased reaction severity, increased morbidity, a greater likelihood of biphasic reactions, and an increased risk of fatality even in some cases in which the initial symptoms were mild. Nowak et al. J Emerg Med ; 45(2):

26 Emergency Management -- Epinephrine It is important to recognize that there is a broad spectrum of anaphylaxis presentations that require clinical judgment in any given patient. The management of a patient who presents with symptoms of anaphylaxis 15 minutes after exposure to the suspected trigger might be handled differently than the patient who was exposed 2 hours previously. Because anaphylaxis can be self-limited, patients can present at a point when symptoms have nearly resolved and might no longer require epinephrine for acute management. -- Practice parameter developed by a joint task force representing AAAAI, American College of AAI, and the Joint Council of AAI. Campbell 2014 AAAI

27 Route of Epinephrine IV bolus epinephrine = BAD IDEA! Reports of death following IV epi Can cause lethal pulmonary edema Can cause lethal arrhythmias Should be used only if cardiopulmonary arrest, per arrest algorithms IV epi drip OK -- continued sx after multiple IM doses Guidelines: use if profoundly hypotensive, after failing multiple IM doses Add: ongoing severe respiratory distress

28 Emergency Management Adjunctive Treatments IV fluids for shock Can lose 35% of circulating blood volume in <10 mins 2 large bore IVs Anticipate rapid changes, early/late symptoms Trendelenburg if hypotensive or ill or post-epinephrine Sitting if resp distress Lateral if vomiting Intubation?

29 What do you want to do for our case? Weight 11 kg What drug? Epinephrine What concentration? 1:1,000 What is his dose? 0.11 mg (0.01 mg/kg) What route? Intramuscular (IM) What location? Lateral thigh

30 Epinephrine What if you only have 1:10,000 epinephrine? short SQ needles? racemic epinephrine? epinephrine that got too hot? epinephrine that got too cold? expired epinephrine?

31 Emergency Management Adjunctive Medications Antihistamines (H1 blockers) act as inverse agonists -- stabilize the inactive form of the H1-receptor on mast cells and basophils. Diphenhydramine (Benadryl), Cetirizine H1 blocker remember those epithelial and smooth muscle receptors? Antacids (H2 blockers) stabilize the inactive form of the H1-receptor on mast cells and basophils remember those cardiac, gastric & epithelial receptors?

32 Antihistamines Onset Duration Sedation Diphenydramine mins 6-8 hours 29% Cetirizine mins 24 hours 17% Similar -- time to resolution of hives -- time to resolution of itching 2 nd generation less sedating, less anticholinergic effect Park 2011 J Allergy Clin Imm

33 Emergency Management Adjunctive Medications Corticosteroids Value not established 4-6 hours to fully take effect Cochrane systematic review: no evidence for or against Recently published abstract: Benefit in admitted patients Decreased length of stay Decreased epi after 1 st day No benefit in discharged patients Choo et al. Cochrane 2010 Michelson et al. PAS meeting 2015

34 Bi-phasic Reactions 1% - 23% of anaphylaxis 8 hours after exposure 4 hours after epi Next morning Up to 25% of fatal and near-fatal food reactions Children: 15%, 75% within 6 hours of ingestion

35 After Epinephrine Anaphylaxis Epinephrine = 911/transport/observe for 4 hours Indications for Extended Observation Severe reaction of slow onset History of previous biphasic reaction Marked asthmatic component Slow response to treatment Ingested antigen (continuous absorption) Long distance from care

36 Key Instructions Take your medications as prescribed Carry an epinephrine auto-injector Avoid the allergen Recognize a reaction See an allergist

37 Autoinjector Comparison Epipen Generic for Adrenaclick Auvi-Q / Allerject Where available in North America U.S. and Canada U.S. U.S. and Canada Location of safety guard opposite needle both ends needle end Verbal instructions no no yes Rests against thigh prior to injection no yes yes Needle self-retracts after injection no no yes Needle is covered on removal yes no yes Time to needle removal from thigh, if used per instructions 10 seconds 10 seconds <2 seconds Fits in a typical pocket no no yes 2nd dose available in a single device no no no Packaged with a trainer device (U.S.) yes no yes Pharmacy wholesale aquisition costs * (0.3 mg dose, 2 devices +/- trainer) Pharmacy wholesale aquisition costs ** (0.3 mg dose, 1 device) * at Seattle Children's Hospital in 2015 ** at Stollery Children's Hospital (Edmonton) in 2015 $ $ $ $89.42 N/A $85.18

38 Tips for Parents Books Food Allergies for Dummies How to Manage Your Child's Life-Threatening Food Allergies: Practical Tips for Everyday Life The Peanut Allergy Answer Book From Confusion to Confidence: KFA's Starter Guide to Parenting a Child with a Food Allergy Other Printed Resources FARE care plan (English and Spanish) FARE Food Allergy Field Guide (English only) FDA food facts (English and Spanish)

39 Tips for Parents Websites: FoodAllergens/ucm htm

40 Tips for Parents Other Blogs:

41 Tips for Parents Facebook Support Groups: Many! Specific to allergens and circumstances, e.g.: No Nuts Moms Food Allergy Network Parents/Families of Children with Severe Food Allergies Multiple Food Allergies R Us FARE

42 Devices and needles Auvi-Q (0.3 mg) Firing Demo Auvi-Q (0.15 mg) Firing Demo Allerject (0.3 mg) Firing Demo EpiPen Firing Demo EpiPen Jr Firing Demo Generic for Adrenaclick Firing Comparison of Needle Properties of Generic epinephrine, EpiPen and Auvi-Q devices While Firing The Window of an EpiPen is Slightly Cloudy Auvi-Q Safety Guard Shouldn't Go Back On

43 Devices and needles Naked EpiPen Firing Demo Naked EpiPen Jr Firing Demo Naked Old-style EpiPen Jr Firing Demo Quick-draw Auvi-Q 0.3mg Firing Demo Quick-draw Auvi-Q 0.15mg Firing Demo AuviQ Dissected -- Improved detail Auvi-Q Still Works Without A Battery EpiPen Wilderness Medicine Technique for Obtaining Additional Epinephrine Doses

44 Devices and needles Search YouTube for epipen firing then click Julie Brown, or

45 Other Pearls for Parents: 504 plan for School Practice, practice, practice Plan how you will restrain your child Give epinephrine first, call 911 second With a hx of anaphylaxis: Do not wait or hesitate Do not fear epinephrine Do not try antihistamines first

46 Summary Allergies are increasing. They are most common in children but can happen at any age. For most people, the only treatment is avoidance, which is challenging. A tiny amount of allergen can be life-threatening. Anaphylaxis is a severe life-threatening reaction, with variable presentations. The severity of previous reactions does not predict the severity of subsequent reactions. Most anaphylaxis happens within an hour of exposure.

47 Summary IM epinephrine is the first line treatment for anaphylaxis. Early use of epinephrine in anaphylaxis is associated with improved outcomes. IV bolus epinephrine only per cardiac arrest guidelines. IV drip epinephrine for persistent or unresponsive anaphylaxis. All other anaphylaxis treatments are adjunctive. Nothing should delay the use of epinephrine. Beware of biphasic reactions.