Anaphylaxis in Anesthesia Study Guide.docx

**Anaphylaxis in Anesthesia** Most Common Culprits - Abx (most common in US) - NMBs (2^nd^ most common in US; most common in UK) - Latex - CHG - Blood Products **Drugs Involved in Perioperative Anaphylaxis** **Substance** **Incidence of Perioperative Anaphylaxis (%)**...

**Anaphylaxis in Anesthesia** Most Common Culprits - Abx (most common in US) - NMBs (2^nd^ most common in US; most common in UK) - Latex - CHG - Blood Products **Drugs Involved in Perioperative Anaphylaxis** **Substance** **Incidence of Perioperative Anaphylaxis (%)** **Most Commonly Associated With Perioperative Anaphylaxis** ---------------------- ------------------------------------------------ -------------------------------------------------------------- Muscle relaxants 69.2 Succinylcholine, rocuronium, atracurium Natural rubber latex 12.1 Latex gloves, tourniquets, Foley catheters Antibiotics 8 Penicillin and other β-lactams Hypnotics 3.7 Propofol, thiopental Colloids 2.7 Dextran, gelatin Opioids 1.4 Morphine, meperidine Other substances 2.9 Propacetamol, aprotinin, chymopapain, protamine, bupivacaine Types of Allergic Reactions - **60% are Type I (IgE) (Most Common)** +-----------------+-----------------+-----------------+-----------------+ | - **Category* | **Etiology** | **Activated | **Injury** | | * | | Immune Cells** | | +-----------------+-----------------+-----------------+-----------------+ ------------------------------------------------- -------------- ----------------------------------------- ------------------------------------------------------------------------------------------- **Type I, immediate hypersensitivity reaction** IgE-mediated Helper T (T\_H2), Mast cells, Basophils Allergic reaction: local (atopic) inflammation; systemic (anaphylactic); life-threatening ------------------------------------------------- -------------- ----------------------------------------- ------------------------------------------------------------------------------------------- ----------------------------------------- ---------------------- ------------ ---------------------------------------------------------------------------- **Type II, antibody-mediated reaction** IgG- or IgM-mediated Macrophage Reaction against normal \"self\" antigens; opsonization and lysis of cells ----------------------------------------- ---------------------- ------------ ---------------------------------------------------------------------------- ------------------------------------------------- ----------------------- ------------------------- --------------------------------------------------- **Type III, immune complex--mediated reaction** IgG- and IgM-mediated Complement, Neutrophils Deposition of insoluble antigen--antibody complex ------------------------------------------------- ----------------------- ------------------------- --------------------------------------------------- --------------------------------------------- ----------------- ------------------------------ --------------------------------------------- **Type IV, cell-mediated hypersensitivity** T cell-mediated CD8 T lymphocytes, CD4 T\_H1 Inflammatory response leading to cell lysis --------------------------------------------- ----------------- ------------------------------ --------------------------------------------- Type I (IgE) mediated Reactions - Type I reactions are anaphylactic or immediate-type hypersensitivity reactions - Antigen binds to membranes of mast cells and basophils - Substance is seen as foreign-\>causes *degranulation* of mast cells and basophils -\>release of chemical mediators from the cells - **Histamine -\> vasodilation** - **Prostaglandin D2 -\> bronchoconstriction** - **Tryptase** - Reaction is initially localized but can quickly spread as allergen enters the bloodstream - **Vasodilation** - **Bronchial Constriction** - **Vascular permeability** - **Can be fatal** Pathophysiology - **Complement activation** is a cascade of reactions to eliminate pathogens and fight infection - These reactions "complement" the activity of antibodies - Complement activation can occur as part of antibody response OR can be activated in the absence of antibodies - Three pathways: all can occur independent of one another - [Classical Pathway]: involves antigen:antibody complexes -\> complement activation - [MB-Lectin Pathway]: lectin binds to pathogen -\> complement activation - [Alternative Pathway]: a spontaneously activated complement binds to the surface of an antigen - All cause release of potent mediators: histamine, prostaglandins, leukotrienes, kinins, serotonin, heparin - All ultimately lead to uptake and destruction of pathogens by phagocytes - AGENTS CAN CAUSE REACTIONS BY MORE THAN ONE MECHANISM - INITIAL MANAGEMENT OF REACTIONS IN ANESTHESIA SETTING IS THE SAME NMBAs - Paralytics have been reported as being responsible for 50-70% of allergic reactions under anesthesia (Nagelhout) - Quaternary ammonium is probably the culprit - 1^st^ exposure may cause sensitization and second can cause anaphylaxis - Most commonly **succinylcholine** but rocuronium is also a culprit - Sugammadex may reverse anaphylaxis by binding to rocuronium - Atracurium causes histamine release -- not necessarily anaphylaxis Sugammadex - Sugammadex is a cyclodextrin that encapsulates and inactivates steroidal NMBAs (Roc,Vec) - Reduces amount of NMBA in plasma and at NMJ rapid reversal of neuromuscular blockade - Incidence of anaphylaxis: 1:3500 -- 1:20,000 to 1:64,000 depending on source - Usually occurs within 1 min of administration - Can occur with first-time administration - Can cause significant airway edema and bronchospasm -\> reintubation prn Antibiotics - Penicillin is responsible for 70% of allergic reactions in general population; Beta-lactam - PCN allergy -- Ancef may have a reaction as well - 8-10 % cross reactivity - Similar beta-lactam ring - May use 2^nd^ and 3^rd^ gen cephalosporins cautiously if patient had allergy to PCN - Avoid use if patient anaphylactic to PCN - Vancomycin- infuse slowly to avoid "Red Man" or "Red Neck" Syndrome" (pruritis, flushing, and erythema of head and upper torso, hypotension) Latex - About **20%** of perioperative allergies are from latex - "Latex fruit syndrome" (allergy to banana, kiwi, mango, chestnut, avocado, passion fruit) - Chronic exposure to latex (*healthcare workers and those undergoing frequent procedures*) increases risk; Less latex is used today so allergic reactions are less common - If there is a history of latex allergy, establish a latex-free environment; Use nonlatex surgical gloves - Consider scheduling as first case of the day; could be aerosolized by prior procedures - Do not insert a needle through any multiple-dose vial with a natural rubber stopper Skin Prep and Contrast Dye - Iodine and chlorhexidine have potential to cause allergy - Dyes, mainly used by surgeons during surgery (*e.g*., for sentinel node mapping) can also cause anaphylaxis Opioids - Common cause of flushing and urticaria following IV administration - Rarely cause life-threatening reactions - Morphine or meperidine can cause degranulation of mast cells and release of histamine - Can (rarely) cause angioedema, bronchospasm, hypotension Propofol - Anaphylaxis 1 in 30,000 - People with egg or soy allergies are **NOT** more susceptible to anaphylaxis with propofol Fluids - Blood and colloids may also cause anaphylaxis - Blood should be typed and crossmatched, verified and monitored to prevent anaphylaxis - Dextran, Hetastarch, Albumin - Gelatin (alpha-gal Other Agents - Radiocontrast dye - NSAIDs - Bacitracin (irrigation solutions) - Metabisulfates and bisulfites (preservatives) - Streptokinase or urokinase - Insulin - Local Anesthetics - Protamine - Aprotinin - Heparin Alpha-Gal Syndrome - Anaphylaxis attributed to animal-derived products may be caused by allergy to the carbohydrate moiety **galactose-alpha-1,3-galactose (also called alpha-gal)** - Gelatin-based colloids - Bovine or Porcine heart valves - Heparin - Hemostatic agents derived from gelatin (gelfoam powders, sponges) - Has been reported in Southeastern U.S., Europe, Asia, Australia - Alpha-gal is present in the tissues of all mammalian species except catarrhines (i.e. humans) - Catarrhines can develop an allergy to tissues and material derived from other mammals - Suspect alpha-gal if patients report delayed allergic reactions following ingestion of mammalian meats, most commonly beef, pork, and lamb. - Reactions range in severity from transient urticaria to anaphylaxis and are typically delayed by several hours. Anaphylaxis Prevention - ASK the patient about drug, food and environmental allergies and consider cross-reactivity! - Patients with a history of allergic reactions (including nondrug allergies) have a higher risk of anaphylaxis during anesthesia - [Risk Factors]: - prior history of anaphylaxis or hypersensitivity reactions, - female sex, - mast cell disorders, - multiple past surgeries or procedures (NMBAs, latex), - asthma, - eczema, - hayfever - Allergic reactions are also more common in patients with a - fish allergy, - prior protamine administration, - or after treatment with protamine-zinc insulin (NPH insulin) Recognizing Anaphylaxis Under Anesthesia \*More likely to present as circulatory collapse under anesthesia\* **Triad: HoTN, Tachycardia, Bronchospasm** **Serum Tryptase immediately after event and 24hrs after event** **Table 9-3 Recognition of Anaphylaxis During Regional and General Anesthesia** **Systems** **Symptoms** **Signs** ---------------- --------------------------------------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Respiratory Dyspnea, Chest discomfort Coughing, Wheezing, Sneezing, Laryngeal edema, Decreased pulmonary compliance, Fulminant pulmonary edema, Acute respiratory failure Cardiovascular Dizziness, Malaise, Retrosternal oppression Disorientation, Diaphoresis, Loss of consciousness, Hypotension, Tachycardia, Dysrhythmias, Decreased systemic vascular resistance, Cardiac arrest, Pulmonary hypertension Cutaneous Itching, Burning, Tingling Urticaria (hives), Flushing, Periorbital edema, Perioral edema Treatment +-----------------------------------------------------------------------+ | Initial Therapy: | | | | 1. Stop administration of antigen | | | | 2. Maintain airway and administer 100% O2 | | | | 3. Discontinue all anesthetics | | | | 4. Start IV volume expansion (2-4 Liters of crystalloid / colloid w/ | | hypotension) | | | | 5. Given Epinephrine (5-10 mcg IV bolus with hypotension, titrate as | | needed; 0.1-1.0 mg IV for cardiovascular collapse | +=======================================================================+ | Secondary Treatment: | | | | 1. Antihistamines (0.5 -- 1mg/kg diphenhydramine) | | | | 2. Catecholamine infusions (Starting doses: Epinephrine 4-8 mcg/min; | | norepinephrine 4-8 mcg/min) | | | | 3. Bronchodilators: inhaled albuterol, terbutaline, and/or | | anticholinergic agents with persistent bronchospasm | | | | 4. Corticosteroids (0.25-1g hydrocortisone; alternatively 1-2g | | methylprednisolone) | | | | 5. Airway evaluation before extubation | | | | 6. Refractory shock: Vasopressin and additional | | monitoring/echocardiography | +-----------------------------------------------------------------------+ Referral for Allergy Evaluation - Patients experiencing suspected **anaphylaxis** should be evaluated! **4-6 weeks after event.** - Will need [detailed] records! - Detailed description of event - S&Sx - Anesthesia and surgical reports - Timing of symptoms in relation to drugs/blood products/ dyes administered - Serum tryptase levels if available - Disinfectants used on surgical instruments - Use of any sterilizing agents (chlorhexidine) - Catheters and stents - Gelatin-containing volume expanders - Hemostatic agent (Surgicel, etc. ) Differential Diagnosis **Other causes of isolated respiratory or airway symptoms** - Acute bronchospasm/asthmatic reaction - Air embolus - Aspiration - Endotracheal tube malposition - Postextubation stridor - Pulmonary edema - Tension pneumothorax - Transfusion-related acute lung injury (TRALI) **Other causes of hypotension/vasoplegia** - Arrhythmias - Cardiac tamponade - Cardiogenic shock - Hemorrhage - Overdose of vasoactive drugs - Partial sympathectomy from spinal/epidural anesthesia - Pulmonary embolus - Sepsis - Vasovagal reaction - Venous air embolism **Note:**\ The differential diagnosis of an allergic or anaphylactic reaction during or following general anesthesia includes a broad list of reactions and physiologic events. Tryptase levels should be *normal* in all of these other disorders to rule out anaphylaxis. Review: Usual symptom onset 5-10 min Latex 30-60 min Roc most likely over opioids, protamine, heparin Muscle relaxants or ABX most common in periop setting Pretreatment w/ steroids and Benadryl before contrast dyes Known sensitivity to sulfites use prop w/o metasulfates Allergy to LA is rare Allergy to amide LA can use Ester What med to treat anaphylaxis first EPI Should bronchospasm from anaphylaxis be treated with Volatiles no, use albuterol (avoid myocardial depressants. Most likely to have Latex allergy? healthcare workers