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“Excuse Me, Is this Allergen Free?”
The Food Allergy Phenomenon and its Anesthesia Implications
Gena L Burnett, CRNA, MSN, BSN, BA
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?
Q&ABelow I have listed food allergies/reaction. If a patient presents with the allergy, would you administer propofol? 1. Peanut – rxn: anaphylaxis2. Soy – rxn: vomiting/rash 3. Egg – rxn: hives4. Egg – rxn: profuse vomiting/diarrhea (FPIES)
Innate and Adaptive Immunity
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
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
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
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
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 IImmediate
Anaphylaxis
Type IICytotoxic
Type IIIImmune Complex
Type IVDelayed
Hypersensitivity
Hypersensitivity
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
Vasoactive mediators released during Antigen/Antibody-Induced Degranulation
Mediator Physiologic EffectHistamine Increased capillary
permeability, peripheral vasodilation, bronchoconstriction
Leukotrienes Increased capillary permeability, intense bronchoconstriction, negative inotropy, coronary artery vasoconstriction
Prostaglandins BronchoconstrictionEosinophil 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
Anaphylactoid Reactions
BerriesShellfish
Mast CellsBasophils
Mediator release
• Non-IgE• No prior sensitization required• Presents as Anaphylaxis• Managed the same way as Anaphylaxis
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
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
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
OASFPIES
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
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
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)
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”
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]."
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!
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?
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
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
CNN.com reports (10/27/2016) Auvi-Q to re-enter market in first half of 2017
FPIESFood 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
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
FPIES ManagementTrigger 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 FoodPreschool – 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)
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?
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
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
EoE and Anesthesia Upper Endoscopy/Biopsy Foreign Body Extraction Esophageal Dilation Pediatric G-tube placement
Concerns?
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
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, Zucchiniwww.latexallergyresources.
org
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
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
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
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
Q&ABelow I have listed food allergies/reaction. If a patient presents with the allergy, would you administer propofol? 1. Peanut – rxn: anaphylaxis2. Soy – rxn: rash/vomiting 3. Egg – rxn: hives4. Egg – rxn: FPIES5. Milk – rxn: causes EoE
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
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
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.
Our FPIES Journey 6mo 7mo 10mo 2.5yr 3yr
Questions, Comments, or References
Email: [email protected]