“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: genaleeburnett@gmail.com