Anaphylaxis.pptx

Anaphylaxis

1. Anaphylaxis Understanding, Recognition, and Management Turki M. Alanazi

2. Objectives What is anaphylaxis ? H ow does it presents ? How to diagnose it ? How to manage it ?

3. Introduction In industrialized countries, the estimated lifetime prevalence of anaphylaxis from all causes is between 0.05 and 2 percent in the general population, and the rate of occurrence is increasing. Anaphylaxis is a systemic reaction that could be mediated by immunologic as well as non-immunologic mechanisms.  It most often results from immunoglobulin E ( IgE )-mediated reactions to foods, drugs, and insect stings, but any agent capable of inciting a sudden, systemic degranulation of mast cells can induce it. Diagnosis is clinical and laboratory evaluation is rarely required.

4. What is Anaphylaxis ?  Anaphylaxis is a serious systemic hypercreativity reaction that is usually rapid in onset and may cause death. Severe anaphylaxis is charactered by potentially life-threatening compromise in airway, breathing and/or the circulation, and may occur without typical skin features or circulatory shock being present. (World Health Organization International Classification of Diseases 11th Edition) Anaphylaxis is a clinical diagnosis that can present with any combination of symptoms affecting various organ systems. The clinical presentation and severity of symptoms differ among individuals and may change over time within the same individual.

5. Immunologic triggers ( IgE -independent mechanism) IgG dependent (rare; eg , to high-molecular-weight dextran, infliximab) Coagulation system activation ( eg , heparin contaminated with oversulfated chondroitin sulfate) Idiopathic anaphylaxis Consider the possibility of a hidden or previously unrecognized trigger Consider the possibility of a mast cell activation syndrome, including systemic mastocytosis Nonimmunologic triggers (direct activation of mast cells and basophils) Physical factors (eg, exercise ¶ , cold, heat) Medications (eg, opioids, NSAIDs) Radiocontrast agents Alcohol (ethanol; may augment, rarely induces) Allergens ( IgE -dependent immunologic mechanism) Foods, especially peanut, tree nut, crustacean shellfish, finned fish, cow's milk, hen's egg Insect stings ( eg , Hymenoptera venom) and insect bites ( eg , kissing bugs) Medications (eg, antibiotics, NSAIDs) Biologic materials, including allergen immunotherapy, monoclonal antibodies, chemotherapy agents, and vaccines* Natural rubber latex Food additives, including spices, insect-derived colorants (eg, carmine), and vegetable gums Inhalants (rare; eg, horse dander, cat dander, grass pollen) Human seminal fluid (rare trigger of anaphylaxis in women) Occupational allergens ( eg , stinging insects, natural rubber latex)

6. PATHOPHYSIOLOGY First exposure Activation of TH2 cell → Stimulate IgE switching Allergen TH2 Cell B Cell

7. First exposure IgE production IgE secreting B cell IgE

8. First exposure IgE bind to mast cell Mast cell Fc ɛRI IgE

9. Second exposure Recognition Allergen Mast cell Fc ɛRI IgE

10. Second exposure Activation of mast cell to release histamine and other mediators Allergen Mediators Mast cell Fc ɛRI IgE

11. What are the Symptoms of Anaphylaxis ? Cutaneous/mucosal (80% to 90%) Respiratory (70%) Gastrointestinal (45%) Circulatory (45%)

12. How to diagnose it ? Anaphylaxis is highly likely when any ONE of the following three criteria is fulfilled: 1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula) AND AT LEAST ONE OF THE FOLLOWING: A. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, hypoxemia) B. Reduced BP* or associated symptoms of end-organ dysfunction ( eg , hypotonia, collapse, syncope, incontinence) 2. TWO OR MORE OF THE FOLLOWING that occur rapidly  after exposure to a LIKELY allergen for that patient  (minutes to several hours): A. Involvement of the skin mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula) B. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, hypoxemia) C. Reduced BP* or associated symptoms (eg, hypotonia, collapse, syncope, incontinence) D. Persistent gastrointestinal symptoms ( eg , crampy abdominal pain, vomiting) 3. Reduced BP*  after exposure to a KNOWN allergen for that patient  (minutes to several hours): A. Infants and children - Low systolic BP (age-specific)* or greater than 30% decrease in systolic BP B. Adults - Systolic BP of less than 90 mmHg or greater than 30% decrease from that person's baseline

13. Anaphylaxis is a clinical diagnosis, and treatment cannot await laboratory confirmation. When the cause of the observed symptoms is in doubt, treatment for anaphylaxis is initiated. The clinical diagnosis can sometimes be retrospectively supported by documentation of elevated concentrations of serum or plasma total tryptase or plasma histamine, although the results of these tests are not immediately available to the treating clinician. It is critical to obtain blood samples for measurement of these mast cell and basophil mediators soon after the onset of symptoms because elevations are transient.

14. Temporal patterns  —  Anaphylaxis is usually characterized by a defined exposure to a potential cause, followed usually within seconds to minutes but rarely up to hours later, by rapid onset, evolution, and ultimate resolution of symptoms and signs. Uniphasic anaphylaxis  —  Uniphasic anaphylactic reactions are the most common type, accounting for an estimated 80 to 94 percent of all episodes. A uniphasic response typically peaks within hours after symptom onset and then either resolves spontaneously or after treatment, usually within several hours Biphasic anaphylaxis  —  Biphasic anaphylaxis is defined as a recurrence of symptoms meeting anaphylaxis diagnostic criteria that develops within 1 to 48 hours following the apparent resolution of the initial anaphylactic episode with no additional exposure to the causative agent occur in about 5 percent of cases. Recurrent symptoms typically occur within 12 hours after resolution of the initial symptoms. Protracted anaphylaxis  —  A protracted or persistent anaphylactic reaction lasts hours to days without clearly resolving completely. . Refractory anaphylaxis  — the persistence of anaphylaxis following appropriate  epinephrine  dosing with three or more appropriate doses of epinephrine or initiation of an intravenous epinephrine infusion along with symptom-directed medical management ( eg , intravenous fluids for hypotension). Delayed anaphylaxis  —  The onset of anaphylaxis can be delayed ( ie , beginning hours rather than minutes after exposure to the causative agent) as can be observed in cases of alpha-gal syndrome, an increasingly recognized food allergy

15. How to manage it ? Acute management: in a hospital setting. The first and most important therapy in anaphylaxis is epinephrine. There are  NO absolute contraindications to epinephrine  in the setting of anaphylaxis. Airway –  Immediate intubation if evidence of impending airway obstruction from angioedema. Delay may lead to complete obstruction. Intubation can be difficult and should be performed by the most experienced clinician available. Cricothyrotomy may be necessary.

16. IM epinephrine (1 mg/mL preparation)  Epinephrine 0.01 mg/kg should be injected IM in the mid-outer thigh. For large children (>50 kg), the maximum is 0.5 mg per dose. If there is no response or the response is inadequate, the injection can be repeated in 5 to 15 minutes (or more frequently). If epinephrine is injected promptly IM, patients respond to 1, 2, or, at most, 3 injections. If signs of poor perfusion are present or symptoms are not responding to epinephrine injections, prepare IV epinephrine for infusion.

17. For pediatric patients, administration of epinephrine into the anterolateral thigh is preferred to the deltoid region as this likely decreases the risk for inadvertent intraosseous administration due to needle length. Intra- venous administration of epinephrine is also not recommended as first-line treatment of acute anaphylaxis, even in a medical setting, due to risk for cardiac adverse events such as arrhythmias and myocardial infarction However, for patients with inadequate response to intramuscular epinephrine and intrave - nous saline, intravenous epinephrine can be given by continuous infusion by microdrip , preferably using an infusion pump in a monitored hospital setting.

18. Place patient in recumbent position , if tolerated, and elevate lower extremities. Oxygen –  Give 8 to 10 L/minute via facemask or up to 100% oxygen, as needed. Normal saline rapid bolus –  Treat poor perfusion with rapid infusion of 20 mL/kg. Reevaluate and repeat fluid boluses (20 mL/kg), as needed. Massive fluid shifts with severe loss of intravascular volume can occur. Monitor urine output. Albuterol –  For bronchospasm resistant to IM epinephrine, give albuterol 2.5 mg inhaled via nebulizer. Dilute in saline if using a concentrated albuterol solution (≥0.5%). Repeat, as needed. H1 antihistamine –  Consider giving diphenhydramine 1 mg/kg (maximum 50 mg IV, over 5 minutes) or cetirizine (children aged 6 months to 5 years can receive 2.5 mg IV, those 6 to 11 years of age can receive 5 or 10 mg IV, over 2 minutes). H2 antihistamine –  Consider giving famotidine 0.25 mg/kg (maximum 20 mg) IV, over at least 2 minutes. Glucocorticoid –  Consider giving methylprednisolone 1 mg/kg (maximum 125 mg) IV. Monitoring –  Continuous noninvasive hemodynamic monitoring and pulse oximetry monitoring should be performed. Urine output should be monitored in patients receiving IV fluid resuscitation for severe hypotension or shock.

19. Glucocorticosteroids are commonly used in anaphylaxis, with the objective of preventing protracted symptoms, in particular in patients with asthmatic symptoms, and also to prevent biphasic reactions ( eg , intravenous hydrocortisone, or methylprednisolone). However, there is increasing evidence that glucocorticosteroids may be of no benefit in the acute management of anaphylaxis, and may even be harmful; their routine use is becoming controversial.

20. Epinephrine infusion –  In patients with inadequate response to IM epinephrine and IV saline, give epinephrine continuous infusion at 0.1 to 1 microgram/kg/minute, titrated to effect. Vasopressors –  Patients may require large amounts of IV crystalloid to maintain blood pressure. Some patients may require a second vasopressor (in addition to epinephrine). All vasopressors should be given by infusion pump, with the doses titrated continuously according to blood pressure and cardiac rate/function monitored continuously and oxygenation monitored by pulse oximetry. Glucagon –  Patients on beta blockers may not respond to epinephrine and can be given glucagon 20 to 30 micrograms/kg (maximum 1 mg) IV over 5 minutes. Rapid administration of glucagon can cause vomiting. Treatment of refractory symptoms:

21. Disposition Observation 2 to 6 hours of is safe for children treated for anaphylaxis without complications. Admission : patients who do not respond promptly to intramuscular (IM)  epinephrine , require more than one dose of epinephrine,. received epinephrine only after a significant delay (>60 minutes) as these features may be risk factors for a biphasic response  Discharge care  —  All patients who have experienced anaphylaxis should be sent home with the following: An anaphylaxis emergency action plan At least one  epinephrine  autoinjector in hand or a prescription for two epinephrine autoinjectors and instructions to fill the prescription immediately Printed information about anaphylaxis and its treatment (Documented) advice to follow up to an allergist, with a referral if possible

22. Confirming the triggers of anaphylaxis  Confirming the diagnosis of anaphylaxis   

23. Summary

24. References UpToDate Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. Netter’s Pediatrics.