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Excuse Me, Is this Allergen Free


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Gene Burnett, NCANA 2016 Annual Meeting

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Excuse Me, Is this Allergen Free

  1. 1. “Excuse Me, Is this Allergen Free?” The Food Allergy Phenomenon and its Anesthesia Implications Gena L Burnett, CRNA, MSN, BSN, BA
  2. 2. Objectives  Describe Elements of:  Immunity - Innate vs. Acquired (Adaptive)  Hypersensitivity reactions  Anaphylaxis  Cross-Reactivity  Understand Food Allergy Basics  Symptoms  Diagnosis  Treatment  Define Differences and give Anesthesia considerations for:  IgE Allergies  FPIES (Food Protein-Induced Enterocolitis Syndrome)  EoE (Eosinophilic Esophagitis)  Oral-Allergy Syndrome (OAS)  Latex-Fruit Syndrome  Food Allergies and Anesthesia Safety – Can we safely administer Propofol?  NPO Guidelines and Food Allergies – are we following the guidelines?
  3. 3. Q&A Below I have listed food allergies/reaction. If a patient presents with the allergy, would you administer propofol? 1. Peanut – rxn: anaphylaxis 2. Soy – rxn: vomiting/rash 3. Egg – rxn: hives 4. Egg – rxn: profuse vomiting/diarrhea (FPIES)
  4. 4. Innate and Adaptive Immunity
  5. 5. Innate Immunity  Initial response to any infection: FIRST LINE  Recognizes targets common to many pathogens  No memory  Can fight the same toxin over and over and never realize it  Skin Invasion resistance  Includes skin, epithelium, sneeze, sloughing dead cells, vomit, earwax, mucus, sebaceous fatty & lactic acids, surfactant  Digestive enzymes destroying swallowed organisms  Phagocytosis  Components of Innate Immunity:  Cellular elements: granulocytes, macrophages, monocytes, natural killer lymphocytes, lysozymes  Non-cellular elements: complement complex, acute-phase proteins and proteins of the contact activation pathway
  6. 6. Leukocytes (WBCs) Eosinophils  2.3% of WBCs in body  Phagocytize allergen-antibody complexes  Exhibit chemotaxis  Collect near allergic reactions  Detoxify inflammation produced by basophils/mast cells  Reduce the spread of inflammation Basophils  0.4% of WBCs in body  IgE has a special propensity to bind to basophils (and mast cells) – ½ million molecules of IgE per cell!  IgE antigen-antibody binding causes basophils to rupture and release Heparin, Histamine, Bradykinin, Serotonin, and Lysosomal enzymes  Causes most/many of allergic reaction symptoms
  7. 7. Adaptive Immunity  Also known as “acquired immunity”, or SECOND DEFENSE LINE  Onset is delayed: May take days to react to an unfamiliar antigen  Fights lethal bacteria, toxins, and foreign tissues  Works by forming antibodies and/or lymphocytes  Immunizations create acquired immunity  Capable of developing memory  Leading to allergic reactions  Is more rapidly induced by an antigen when memory is present  Components of adaptive immunity:  Humoral: Mediated by B-lymphocytes (they produce antibodies)  Liver and Bone Marrow  Cellular: Mediated by T-lymphocytes (destroy foreign agents)  Thymus gland
  8. 8. Antigen-Antibody Antigen  Foreign proteins/toxins evoking production of Antibodies  Initiate acquired immunity  Leads to the production of T- lymphocytes via signal transduction Antibody  What the body makes to ‘remember’ a disease/toxin  Also termed immunoglobulins  Every antibody has a unique shape/class (5) IgM, IgG, IgA, IgD, IgE  Antibodies act by:  Direct attack on antigen  Activation of the Complement System  Initiate ANAPHYLAXIS
  9. 9. Excessive Adaptive Immunity: Hypersensitivity Reactions  Time of onset  Immediate hypersensitivity: Antibody mediated  Delayed hypersensitivity: T-Cell mediated  Nature of mediator  Type I: IgE mediated  Type II: IgG or IgM, and complement mediated  Type III: IgG, IgM, and complement mediated  Type IV: Delayed hypersensitivity reactions  Type V: Stimulatory Type I Immediate Anaphylaxis Type II Cytotoxic Type III Immune Complex Type IV Delayed Hypersensitivity Hypersensitivity
  10. 10. How Anaphylaxis Occurs Allergen binds with mast cell antibodies (IgE) Vasoactive mediators released First wave of symptoms Activated mast cells produce cytokines Second wave of symptoms 6 to 8 hours later
  11. 11. Vasoactive mediators released during Antigen/Antibody-Induced Degranulation Mediator Physiologic Effect Histamine Increased capillary permeability, peripheral vasodilation, bronchoconstriction Leukotrienes Increased capillary permeability, intense bronchoconstriction, negative inotropy, coronary artery vasoconstriction Prostaglandins Bronchoconstriction Eosinophil chemotactic factor Attraction of eosinophils Neutrophil chemotactic factor Attraction of neutrophils Platelet activating factor Platelet aggregation and release of vasoactive amines Stoelting Table 29-2
  12. 12. Anaphylactoid Reactions Berries Shellfish Mast Cells Basophils Mediator release • Non-IgE • No prior sensitization required • Presents as Anaphylaxis • Managed the same way as Anaphylaxis
  13. 13. Type IV Hypersensitivity Reaction  A cell-mediated response where sensitized T-cells release cytokines causing tissue damage  Repeated exposure causes activated T-helper and T-cytotoxic cells to move from circulation to the area of toxin (in food allergies, the GI tract)  Non-IgE  FPIES  EoE  Dermatitis
  14. 14. Cross-Reactivity or Cross-Sensitization  90% chance of reacting to other milks with milk allergy  75% chance of reacting between shellfish/crustacean  50% chance of reacting between types of fish  Proteins can react between:  Food to Food  Pollen to Food  Latex to Food Close structural similarities between any two allergens from divergent sources can produce similar allergic reactions in sensitive patients
  15. 15. Food Allergy Basics  Definition: hypersensitive, exaggerated, or adverse immune response towards food proteins causing tissue injury  Presentation  Myriad of symptoms  Wide variation in severity  Age can play a role  Types include:  IgE Mediated  Mixed IgE/Non-IgE  EoE  Non-IgE – cellular/delayed  OAS  FPIES
  16. 16. Food Allergy Testing Options  Medical History and Physical Exam  SPT – Skin Prick Test  IgE specific, non-stand alone  sIgE – Allergen-Specific Serum IgE  Blood draw required, Non-stand alone  APT – Atopy Patch Test  Skin-Contact FA, non-stand alone  FED – Food Elimination Diet  EoE (mixed IgE/non-IgE)  FPIES(non-IgE mediated)  OFC – Oral Food Challenge  When open or single-blind, it must be supported by Pt Hx and Labs  When double-blind placebo-controlled, it is considered diagnostic of FA  Supervised – hospital or office-based and may require IV, labs, etc. NOTE: not all patients with allergic sensitization have a clinical allergy
  17. 17. Types of Food Allergens  Class 1  Primary sensitizers usually through the GI tract  Water-soluble glycoproteins  Heat, acid, and protease stable  Include the ‘Great 8’ and fruits/vegetables  Class 2  Cross-reactivity with Plant Bases  Often leads to Oral Allergy Syndrome or Latex-Fruit Syndrome  Heat Labile/Difficult to isolate
  18. 18. The Great 8 for IgE Allergies  Milk  Egg (usually egg white) Ovalbumin, Ovomucoid, Conalbumin  Soy  Wheat  Peanut (1.1%)  Treenut  Fish/Shellfish (2.3%) ALLERGENS can be found in medications, vaccines, cosmetics, craft materials, sunscreen/bug spray, cleansers, lotions, soaps, and diaper cream (ingredient and cross contamination)
  19. 19. Symptoms of a Reaction: • Mild symptoms may include one or more of the following: • Hives (reddish, swollen, itchy areas on the skin) • Eczema (a persistent dry, itchy rash) • Redness of the skin or around the eyes • Itchy mouth or ear canal • Nausea or vomiting • Diarrhea • Stomach pain • Nasal congestion or a runny nose • Sneezing • Slight, dry cough • Odd taste in mouth • Uterine contractions • Severe symptoms may include one or more of the following: • Obstructive swelling of the lips, tongue, and/or throat • Trouble swallowing • Shortness of breath or wheezing • Turning blue • Drop in blood pressure • Feeling faint, confused, weak, or passing out • Loss of consciousness • Chest pain • A weak or “thread” pulse • Sense of “impending doom”
  20. 20. Reaction Described by Child • Pull or scratch tongue • Put hands in the mouth/Rubbing the face • Hoarse or squeaky voice • Crying • Slurring of words • "This food is too spicy.” • "My tongue is hot [or burning].” • "It feels like something’s poking my tongue.” • "My tongue [or mouth] is tingling [or burning].” • "My tongue [or mouth] itches.” • "It [my tongue] feels like there is hair on it.” • "My mouth feels funny.” • "There's a frog in my throat.” • "There’s something stuck in my throat.” • "My tongue feels full [or heavy].” • "My lips feel tight.” • "It feels like there are bugs in there." (to describe itchy ears) • "It [my throat] feels thick.” • "It feels like a bump is on the back of my tongue [throat]."
  21. 21. IgE Allergy Desensitization  Frequent, repeated intradermal injections of increasing amounts of an allergen may produce tolerance  Mechanism: development of specific IgG antibodies to the allergen  IgG antibodies bind with the allergen as soon as it enters the body preventing it from reacting with the IgE antibodies on the surface of mast cells  IgG coated allergens are then cleared by macrophages  Unfortunately desensitization does not completely eliminate immediate hypersensitivity reactions, they reduce symptoms  Further, life-threatening anaphylaxis has been known to occur from desensitization therapy itself!
  22. 22. Anesthesia and Anaphylaxis  Dramatic hypotension and CV collapse may be the only signs under general anesthesia  Vasodilation  Decreased Tissue Perfusion  Shock  Bronchospasm  Laryngeal Edema  Vomiting/Esophageal Spasm  Most reactions occur within 5-10 minutes  Proof of anaphylaxis: Increased plasma tryptase within 1-2 hours of the suspected event  Pre-administered antihistamines to mask IgE-mediated anaphylaxis? No  Plasma histamine returns to baseline within 30-60 minutes of the event  Operating Room treatment (ADULTS):  Discontinue Anesthetic Agents  100% FiO2 – intubate/support ventilation  Treat Hypotension – Fluids, Pressors  Epinephrine – 50-100mcg IV, or 0.5-1mg IV in CV collapse  Antihistamines – H1 Diphenhydramine 50mg IV, H2 Ranitidine 50mg IV  Corticosteroids – Hydrocortisone 250mg-1gm IV vs Methylprednisolone 1-2gm IV  Bronchodilators – Albuterol PRN  Consider postponing extubation – cuff leak?
  23. 23. Anesthesia and Anaphylaxis: Pediatrics WHAT WILL YOU SEE? RASH, BRONCHOSPASM, HYPOTENSION • Increase O2 to 100% • Remove suspected trigger(s) • Ensure adequate ventilation/oxygenation • If HYPOtensive, turn off anesthetic agents • To restore intravascular volume: NS or LR 10-30 mL/kg IV/IO rapidly • To restore BP and ↓mediator release: Epinephrine 1-10 MICROgrams/kg IV/IO, as needed, may need infusion 0.02-0.2 MICROgrams/kg/min • Additionally, can give 10MICROgrams/kg IM for depo effect (lingering effects of Epi after stimulus has been removed) • To ↓ bronchoconstriction Albuterol (Beta-agonists) 4-10 puffs • To ↓ mediator release Methylprednisolone 2 mg/kg IV/IO (MAX 100 mg) • To ↓ histamine-mediated effects: Diphenhydramine 1 mg/kg IV/IO (MAX 50 mg) • To ↓ effects of histamine: Famotidine or Ranitidine 0.25 mg/kg IV- 1 mg/kg IV • If anaphylactic reaction requires laboratory confirmation, send mast cell tryptase level within 2 hours of event
  24. 24. EpiPen/EpiPen JR News  EpiPen (0.3mg) dose vs EpiPen JR (0.15mg) dose  2-pack price changes (480% increase!!)  2004> $83.46  2007> Mylan purchases drug from Merck  10/2015> Sanofi US voluntarily recalls Auvi-Q auto- injector d/t inaccuracies with dose injected  Teva and Adamis auto-injectors not approved by the FDA  2016> $608.61  The New York Times reports (9/16/2016)  Mylan working to have the drug placed on the Federal Preventative List (meaning no co-pay)  Mylan offers a co-pay discount program  Mylan contributes to many political campaigns, patient advocacy groups, and physician groups  reports (10/27/2016)  Auvi-Q to re-enter market in first half of 2017
  25. 25. FPIES Food Protein-Induced Enterocolitis Syndrome  Epidemiology  Non-IgE/T-cell mediated GI food hypersensitivity  Prevalence is unknown, but it is rare (0.3% of population in an Israeli study)  Non-Familial  Some studies report slightly more common in boys (52%-60%)  80% of FPIES children are multiple reactors/atopic  90% of children diagnosed outgrow by age 3  Often begins in infancy with introduction of Cow’s milk/Soy and solid foods (can be delayed in breastfed children)  Triggers  RICE, oat, and barley  Chicken, turkey, and egg white  Green pea  Peanut  Sweet potato, white potato, and corn  Fruit protein  Fish and shellfish
  26. 26. FPIES  During episode, Labs show elevated WBC, acidosis, methemoglobinemia, thrombocytosis, hypoalbuminemia  There are NO diagnostic/predictive tests except OFC  Negative SPTs  Negative sIgE  APT??  Often mis-diagnosed/missed on evaluation and physical exam  Regular follow-up with specialist: GI, Allergist, PT/OT/ST  ACUTE  Repetitive, projectile emesis 1-3hrs after food ingestion  Lethargy  Pallor/Ashen in appearance  Diarrhea with blood/mucous 2- 10hrs after ingestion  Hypothermia  Dehydration  Hypotension/Shock • CHRONIC • Intermittent emesis • Bloody diarrhea • Poor wt gain/wt loss • Failure to Thrive • Abdominal distension • Irritability • Same as Acute
  27. 27. FPIES Management Trigger food elimination/Strict Allergen Avoidance  First Line/Acute  REMEMBER: EpiPen won’t help!  Fluid resuscitation  Single Dose Steroids  Zofran  OFC  Considered the ‘gold-standard’, but are not required for diagnosis  0.15-0.3g protein/kg body weight in 3 doses every 15-20min  50% reactive OFC requires fluid resuscitation via IV  Q18-24months/Follow-Up  Delayed Introduction/At-Home Food Trial  Avoid grains, legumes, and poultry until age 1  Tolerance of one food in each group is often a good indicator of ‘safes’  Soy – legumes  Oat – grains  Chicken - poultry  Breastfeeding partially digests and processes the proteins  Protects against CM/Soy FPIES, but not Solid Food FPIES  Mother’s elimination diets No Sharing Food, No Restaurant Food, No Party Food Preschool – allergy table with teacher supervision & separate preparation ALLERGENS can be found in medication, vaccines, cosmetics, craft materials, bubbles, sunscreen/bug spray, cleansers, lotions, soaps, and diaper cream (ingredient and cross contamination)
  28. 28. Anesthesia and FPIES  Operative Scenario: A 2yo patient with FPIES to milk, rice, oat, and soy presents for endoscopy.  Concerns?  Changes in the plan of care?  Changes in your hand-off procedures?
  29. 29. EoE: eosinophilic esophagitis  Chronic esophageal dysfunction caused by T-cell inflammatory response to food/environmental allergens  Activated eosinophils -> cytokine release -> attack healthy tissue repeatedly -> epithelial/esophageal injury  Endoscopic Features/Histology Reports are characteristic but not diagnostic (6yr delay in diagnosis reported in one study)  Pediatrics – mostly inflammatory; dysphagia (inaccurately described), emesis, abdominal pain, GERD  Adults – both inflammatory and fibrostenosis; dysphagia and food impaction  Most pts have atopic history  IgE food allergies  Allergic Rhinitis  Asthma  Contact Dermatitis COMMON TRIGGERS MILK wheat, egg, soy, nuts, seafood corn, chicken
  30. 30. EoE Treatment  IgE Allergy Testing – SPT, sIgE, APT  Dietary restriction  PEDS: hypoallergenic AA-based formula and minimal OFC added solid foods  Concerns: feeding difficulties (N/OG-Tube, G/J-Tube), fear, isolation  Topical Corticosteroids  Fluticasone (aerosolized/swallowed)  Budesonide (suspension vs nebulizer)  Maintenance?  Esophageal Dilation  New Therapies in Clinical Trials  PPIs  Monoclonal Antibody therapy at IL-5 – Mepolizulab (Nucala) and others  Mast Cell Stabilizer - Cromolyn Sodium  CysLT1 receptor antagonist – Montelukast (Singulair)  Angiotensin II receptor blockers – Losartan
  31. 31. EoE and Anesthesia  Upper Endoscopy/Biopsy  Foreign Body Extraction  Esophageal Dilation  Pediatric G-tube placement
  32. 32. OAS: Oral Allergy Syndrome  Pollen Food Hypersensitivity Syndrome  Considered ‘mild’ IgE reaction limited to the oropharynx  Pruritus  Tingling  Erythema  Swelling of lip, oral mucosa, throat, or tongue  Patient has environmental/pollen allergies and cannot eat fruits/vegetables with pollen allergen on or in the fruit  Most common with raw or uncooked fruit/vegetable  A Class 2 Type of Food Allergy  In 3% of patients, OAS causes systemic reaction or anaphylaxis
  33. 33. Latex-Fruit Syndrome  Food (or seeds) with clinical or immunological cross-reactivity with latex proteins  2002 study shows 30-50% of patients with NRL allergy also have some food hypersensitivities (Wagner and Breiteneder)  IgE vs Non-IgE mediated Food Allergy concerns? • High: Avocado, Banana, Chestnut, Kiwi • Moderate: Apple, Carrot, Celery, Melons, Papaya, Potato, Tomato • Low/undetermined (40): Apricot, Buckwheat, Cassava/Manioc, Castor bean, Cherry, Chick pea, Citrus fruits, Coconut, Cucumber, Dill, Eggplant/Aubergine, Fig, Goji berry/Wolfberry, Grape, Hazelnut, Indian jujube, Jackfruit, Lychee, Mango, Nectarine, Oregano, Passion fruit, Peach, Peanut, Pear, Peppers (Cayenne, Sweet/bell), Persimmon, Pineapple, Pumpkin, Rye, Sage, Strawberry, Shellfish, Soybean, Sunflower seed, Tobacco, Turnip, Walnut, Wheat, Zucchini
  34. 34. Gluten  Gluten is a protein found in grains: wheat, rye, barley, and triticale (wheat/rye cross)  Those with Celiac have to specifically avoid Gluten – even trace amounts can cause a reaction  Those who are symptomatic with gluten but do not have Celiac have Non-Celiac Gluten Sensitivity  Cross-contamination during manufacturing  Vitamins lost with Gluten-Free diet: iron, calcium, fiber, thiamin, riboflavin, niacin, folate
  35. 35. MSG  Monosodium glutamate  A meat flavor enhancer often found in Chinese and Asian foods  Reported System Complex – myalgia, nausea, neck pain, backache, sweating, flushing, chest tightness  Difficult to reproduce in OCTs
  36. 36. Food Allergies and Propofol  Emulsion contains soybean oil, egg lecithin, and glycerol  Soy and Egg Allergy – contamination during processing  Peanut Allergy – cross-reactivity between soy and peanut: review from 2000 shows a low rate of cross-reactivity  Allergy is thought to be IgE mediated with the 2-isopropyl-group as the suspect epitope (multiple studies)  (2001) Australia Peds study: 28 egg-allergic children with 43 propofol cases; one atopic child with egg anaphylaxis got erythema/urticaria, confirmed propofol allergy via SPT/sIgE  (2013) Spanish study: 60 EoE pts had 404 endoscopies with propofol; 86% had IgE to egg, soy, or peanut via SPT/sIgE (35% with clinical allergy); No reactions reported
  37. 37. Food Allergies and Propofol  (2016) Denmark study (BJA):  Study A: 273 pts with suspected intra-op reactions  154 propofol-exposed pts had SPTs and IV challenge  4 pts tested positive for propofol allergy – but none had allergies to egg, soy, or peanut  Study B: 520 pts with +sIgE to egg, soy, or peanut retrospectively reviewed  171 retrieved records from 99pts – no reactions found  “No evidence for contraindications to the use of propofol in adults allergic to egg, soy, or peanut”  (2016) Polish/Czech review of evidence:  ‘References demonstrating safe use of propofol in food allergy pts’  5 retrospective studies, 1 lit review, and 1 consensus statement, includes adults and pediatrics  ‘References demonstrating a potential allergic reaction to propofol’  8 case reports and 1 retrospective study  Limited data does not support avoiding propofol
  38. 38. Q&A Below I have listed food allergies/reaction. If a patient presents with the allergy, would you administer propofol? 1. Peanut – rxn: anaphylaxis 2. Soy – rxn: rash/vomiting 3. Egg – rxn: hives 4. Egg – rxn: FPIES 5. Milk – rxn: causes EoE
  39. 39. NPO Guidelines and Food Allergies ASA Guidelines 2H – clear liquids 4H – breastmilk 6H – non-human milk, formula, light meal 8H – full, high-fat meal NPO after midnight  Likely originated in 1946 with an obstetric study on pulmonary aspiration by Mendelson  1946 study found 0.15% OB patients who received GA had pulmonary aspiration compared to 0.006% in a 2002 study  Gastric volume and/or pH is unrelated to fasting duration Benefits of following Guidelines • Better hydration status • Improved hemodynamic stability • Reduction in surgical stress response Adverse Effects of Prolonged NPO status • Hunger, thirst, discomfort, crying • Hypoglycemia • Dehydration, hypovolemia • Electrolyte imbalance, ketosis • Malnutrition • General malaise • Delayed recovery, wound healing • Immune suppression, infection susceptibility
  40. 40. Evidence-Based Practice or Time-Honored Tradition?  (2002) Crenshaw and Winslow – 155 adults, 14hrs solids, 12hrs liquids  (2008) Crenshaw and Winslow follow-up – 275 adults, 14hrs solids, 11hrs liquids  (2011) Engelhart et. Al – 1350 pediatrics, 12hrs solids, 8hrs liquids  (2013) Arun and Korula (INDIA) – 50 pediatrics, ~11hrs solids, ~9hrs liquids  (2013) Williams et. Al – 219 pediatrics  Average Fasting Times to Surgery/Procedure time  Solids: 14.08+6.28hrs  Breastmilk: 9.82+6.6hrs  Clears: 12.61+5.88hrs  Non-compliance w/ guidelines based on MD order  62% for solids  100% for breastmilk  97% for clears  (2016) Brunet-Wood et. Al – 53 pediatrics  No patients allowed clears 2hrs prior and 70% were NPO for 8+ hrs prior  Found 80% (complex) and 65% (non-complex) of pre-op NPO times not within guidelines  Also covered post-operative NPO times: time to first nutrition in complex cases is 63.6hrs and 23.8hrs for non-complex cases
  41. 41. NPO True or False?  My 64yo patient can have a cup of black coffee at 0600 for hernia surgery at 0900.  The same patient is obese with diabetes and GERD, and added cream to the coffee. What time can the surgery start?  My 18month old patient can have apple juice at 0700 for oral surgery at 0930.  My 5month old patient can be nursed at 0500 for a T&A at 0800.  The ENT surgeon has been delayed and cannot arrive until 1000. It is 0630 and the patient has arrived in pre-op. It is ok for the parent to give the child Pedialyte in a bottle.  As a practitioner, I keep my patients NPO for too long.  Pre-op will page me every 5 minutes if we change the rule NPO after midnight.
  42. 42. Our FPIES Journey  6mo  7mo  10mo  2.5yr  3yr
  43. 43. Questions, Comments, or References Email: