Anaphylactic and Anaphylactoid Reactions

Transcription

1 Anaphylactic and Anaphylactoid Reactions Steve LaFond, PharmD Jill Wall, BSN, CRNI April 27, 2017

2 Objectives Describe anaphylactic and anaphylactoid reactions Understand the mechanism of action in anaphylaxis Describe the risk factors for developing anaphylaxis Describe the clinical manifestations in anaphylaxis Identify management of a patient experiencing anaphylaxis

3 Approximately 1,500 deaths caused by anaphylaxis annually in the U.S.

4 Anaphylaxis Subtypes Drugs Latex Food Insect stings

5 Anaphylactic & Anaphylactoid Reactions Life-threatening events result from overactive and misdirected immune response to a substance (antigen) that is viewed as foreign to the body. Reaction is systemic, involves multiple organ systems, and a direct result of the release of chemical mediators from mast cells and basophils. Limmer DD., Mistovich JJ., Krost WS. (2004, June 1). Anaphylactic and Anaphylactoid Reactions. EMS World. Retrieved from

6 Anaphylactic & Anaphylactoid Reactions Anaphylaxis (allergic reaction) Requires patient to be sensitized and the reaction mediated through IgE antibodies Occurs only after patient has been previously exposed at least once to antigen and is sensitized Limmer DD., Mistovich JJ., Krost WS. (2004, June 1). Anaphylactic and Anaphylactoid Reactions. EMS World. Retrieved from

7 Anaphylactic & Anaphylactoid Reactions Anaphylactoid reaction (nonallergic reaction) Does not need presence of IgE antibodies. Substances initiating the reaction cause a direct breakdown of the mast cell and basophil membranes (e.g., radiopaque contrast media, blood products [e.g., IVIG], NSAIDs, aspirin) Can occur following a single, first-time exposure to certain agents in nonsensitized patients Both produce same clinical manifestations and treated exactly the same. Limmer DD., Mistovich JJ., Krost WS. (2004, June 1). Anaphylactic and Anaphylactoid Reactions. EMS World. Retrieved from

8 World Allergy Organization Recommends replacing anaphylaxis and anaphylactoid with immunologic anaphylaxis (IgE-mediated and non-ige mediated [IgG and immune complex complement-mediated]) and nonimmunologic anaphylaxis (events resulting in sudden mast cell & basophil degranulation in the absence of immunoglobulins), respectively. Shahzad Mustafa, S., Kaliner Michael A., et al. (2017, Feb 22). Anaphylaxis. Retrieved from

9 Mechanisms of Action

10 Mechanisms of Action Sensitization (Anaphylaxis) An immunologic process that occurs when the body views a substance as foreign. In response, IgE antibodies are produced to fight off the substance. IgE antibodies have a strong affinity for mast cells and basophils and attach to receptors on the cell membrane.

11 Mechanisms of Action Mast cells (Anaphylaxis) Located in connective tissue, near blood vessels, in mucosal layer in lungs, and GI tract. Filled with granules that release chemical mediators (e.g., histamine, heparin, proteases, chemokines, cytokines). Basophils Contain granules and are polymorphonuclear leukocytes that circulate in blood; become mast cells

12 Mechanisms of Action (Anaphylaxis) Patient becomes sensitized when IgE antibodies attach to mast cells and basophils. IgE antibodies can stay attached for seconds, minutes, days, weeks, months, or years.

13 Anaphylactic Reaction

14 Mechanisms of Action (Anaphylaxis) With reintroduction of the antigen in a sensitized patient, it attaches to IgE antibodies located on the cell membranes of the mast cells and basophils. This linkage causes breakdown or degranulation of cell membranes, releasing chemical mediators from the cell granules into extracellular fluid. These chemical mediators are responsible for producing the clinical condition found in anaphylaxis.

15 Mechanisms of Action (Anaphylaxis) Histamine Vasodilation, hypotension (increased vascular permeability), flushing, bronchospasm, pruritus, and rhinorrhea Leukotrienes Antihistamine-resistant bronchoconstriction Prostaglandins/Thromboxanes Vasoactive compounds causing bronchoconstriction

16 Mechanism of Action (Anaphylactoid) Complement-mediated by an antigenantibody complex Byproducts of complement cascade (C3a and C5a) and substances called anaphylatoxins Cause mast cell and/or basophil degranulation Similar systemic manifestations as IgEmediated anaphylaxis (thus treated in the same manner)

17 Major Pathophysiologic Factors Most signs & symptoms of anaphylaxis are related to: Increase in vascular permeability Vasodilatation Bronchiole smooth muscle contraction (mostly histamine-mediated)

18 Risk Factors

19 Atopy Risk Factors Genetic tendency to develop allergic diseases Pre-existing allergies Foods, drugs, bee stings, environmental allergies Female Older age Previous exposure to drug Newly diagnosed, untreated patient Circulating lymphocyte counts of 25,000

20 Risk Factors Hematologic malignancies Route, dosing interval, duration of therapy Presence of nonhuman sequences (foreign compounds) Complex chemical structures (e.g., proteins) Albumin, enzyme replacement High-molecular weights (>6000 daltons) Dextran, Humira, Remicade

21 Risk Factors Haptens/aggregates (e.g., antibiotics) Variety of chemicals Drugs, food, perfume Lack of endogenous proteins Bee stings, venoms

22 Clinical Manifestations

23 Signs & Symptoms of Anaphylaxis

24 Clinical Manifestations Cardiovascular Chest pain, palpitations, hypotension, syncope, hypertension, tachycardia, bradycardia, arrhythmia, edema, ischemia or infarction, cardiac arrest Central nervous system Headache, (throbbing), dizziness, anxious, confusion, altered mental status, level of consciousness (LOC)

25 Clinical Manifestations Skin or mucous membranes (80% 90% cases) Children may present more commonly with respiratory symptoms followed by cutaneous Some of most severe cases of anaphylaxis present in absence of skin findings Symptoms range from mild dermatologic complaints to anaphylactic shock to death

26 Clinical Manifestations Dermatologic Rash, pruritus, urticaria, flushing, local or diffuse erythema, conjunctival erythema and tearing, angioedema, warmth Endocrine Rigors, diaphoresis, fever, generalized feeling of warmth

27 Clinical Manifestations Gastrointestinal Nausea, vomiting, metallic taste, diarrhea, abdominal cramping, bloating, dysphagia Genitourinary Incontinence, uterine cramping or pelvic pain, renal impairment Psychiatric Anxiety, sense of impending doom

28 Clinical Manifestations Respiratory Cough, dyspnea, nasal congestion, rhinitis, sneezing, hoarseness, tachypnea, wheezing, chest tightness, hypoxemia, bronchospasm, reduced pulmonary expiratory flow, oropharyngeal or laryngeal edema, stridor, pulmonary infiltrates, cyanosis, acute respiratory distress syndrome

29 Anaphylaxis Clinical Syndrome

30 Management of Reaction

31 Management of Reaction Emergency care Support vital functions while eliminating three primary factors: Vasodilatation Increased vascular permeability Bronchoconstriction

32 Management of Reaction Late-phase or biphasic anaphylaxis can occur up to 72 hours following initial reaction (most occur within 8 to 10 hours) Potential risk factors include severity of initial phase, delayed or suboptimal epinephrine dose(s) during initial phase, laryngeal edema, or hypotension during initial phase Incidence varies from <1% up to 23% of cases

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34 WAO Anaphylaxis Guidelines Even a few minutes delay can lead to hypoxic-ischemic encephalopathy or death The importance of having a management protocol cannot be over emphasized because retention of memorized facts and algorithms can be poor in a crisis and there is little to no time to look up information

35 Prompt Initial Treatment Initial assessment should take less than 1 minute Any indication of airway, breathing, or circulation failure should result in administration of epinephrine and calling 911

36 Assessment Assess airway, breathing, circulation (ABC) LOC/mental status Vital signs (sudden reduced BP, hypotonia, collapse, incontinence) Observe for sudden cutaneous manifestations Urticaria, angioedema, erythema, pruritus, hives, swollen lips-tongue-uvula

37 Assessment Auscultate lungs, listening for stridor/wheezing, SOB Dysphonia, cough, hoarseness, hypoxemia Assess for sudden gastrointestinal symptoms Cramping, abdominal pain, vomiting

38 Interventions Remove exposure to trigger Assess airway, breathing, circulation Administer epinephrine, if needed Call 911 Place patient supine with legs elevated Maintain patent airway (O2, high flow, prn) Maintain IV with 0.9% NS

39 Interventions CPR, if indicated At frequent/regular interval, monitor BP, HR and function, respiratory status, and oxygenation Monitor continuously, if possible

40 Interventions Obtain VS every 2 minutes until stable Administer medications, as needed Provide emotional support to patient/family Keep patient warm Stay with patient Transport via ambulance to hospital

41 Epinephrine

42 Epinephrine WAO Guidelines The evidence base for prompt epinephrine injection in the initial treatment of anaphylaxis is stronger than the evidence base for the use of antihistamines and glucocorticoids in anaphylaxis.

43 Epinephrine Mixed adrenergic agonist (alpha & beta) Alpha-1 adrenergic vasoconstrictor effect in most body organ systems Prevent and relieve airway obstruction caused by mucosal edema (mediated by beta-2 receptor activity) Prevent and relieve hypotension and shock Mitigates anaphylactic response indirectly via camp second messenger system

44 Epinephrine Inject IM as soon as anaphylaxis is diagnosed or strongly suspected Dose 0.01 mg/kg of a 1:1,000 (1 mg/ml) solution to a maximum of 0.5 mg in adults (0.3 mg in children) Depending on severity and response to initial injection, dose can be repeated every 5 15 minutes, as needed

45 Epinephrine Transient pharmacologic effects Pallor, tremor, anxiety, palpitations, dizziness, headache Serious adverse effects Ventricular arrhythmias, hypertensive crisis, pulmonary edema

46 Epinephrine Administration Devices

47 Epinephrine American Academy of Pediatrics recommends epinephrine as a first-line therapy for anaphylaxis Update on Meridian s voluntary worldwide recall of EpiPen autoinjector See - Frellick M. (2017, Feb. 13). AAP Updates Guidance on Epinephrine Use for Anaphylasix. Medscape. Retrieved from -

48 Other Medications

49 Glucocorticoids Some effect on early phase reactions of anaphylaxis, but mostly on mitigating latephase reactions (caused by neutrophils and cytokines) Block transcription of genes that encode cytokines related to the inflammatory pathway Given orally (typically prednisone) for less severe reactions or IV (hydrocortisone or methylprednisolone)

50 Antihistamines (H1 & H2) Not drug of choice for initial anaphylaxis treatment Relieves life-threatening respiratory symptoms or shock Decreases urticaria, pruritus, vascular permeability IV route can cause hypotension if administered too rapidly Diphenhydramine (H1 antagonist) drug-ofchoice dosed at 1 mg/kg up to 50 mg

51 Antihistamines (H1 & H2) Diphenhydramine Can be given IM or IV for treatment, or PO if given as a premedication Hydroxyzine or cetirizine Given PO as a premedication H2 antagonists (e.g., cimetidine or ranitidine) Can be given for more thorough antihistamine effect

52 0.9% Normal Saline Crystalloid solution used to restore intravascular volume (up to 35% loss due to increased vascular permeability) Infuse 1 liter in hypotensive adults or 20 ml/kg in pediatric patients over 15 minutes

53 Case Studies

54 Case Study 1 Elaprase enzyme replacement 5-yo with Hunter syndrome (mucopolysaccharidosis II, MPS II) Developed initial infusion reaction after several previous infusions w/o reaction Symptoms included stridor, wheezing, rigors, fever RN stopped infusion/maintained patency of IV RN administered epinephrine 0.5 mg IM 911 called and transported to hospital

55 Case Study 1 (cont.) Patient recovered and received next 3 infusions in outpatient short stay Patient resumed home therapy 4 weeks later and continued symptom-free for about 4 months Patient experienced more severe reaction cardiorespiratory symptoms including shallow breathing with apneic spells, increased wheezing, hypotension, and bradycardia (from 92 bpm to 55 bpm within 10 minutes)

56 Case Study 1 (cont.) Developed mild fever RN stopped infusion/maintained patency of IV RN administered epinephrine IM 911 called Supported patient in home MD notified Patient transported to hospital by ambulance Patient received infusions in short stay for next 6 months

57 Case Study 2 IVIG administration (nonclassical S & S) Teenage patient with protein-losing enteropathy and immunodeficiency receiving IVIG Patient premedicated with ibuprofen and oral Benadryl Patient developed headache, chills, nausea RN stopped infusion MD notified IV diphenhydramine administered, infusion restarted; tolerated the rest of the infusion Symptoms resolved post-diphenhydramine

58 Case Study 2 (cont.) Next infusion (emesis x1) Infusion stopped, MD contacted, IV diphenhydramine administered Infusion restarted (emesis x1), MD notified, infusion continued, no further emesis, BP slightly elevated IV diphenhydramine premedicated for future infusions No further issues

59 Case Study 3 IV Zosyn antibiotic 19-yo trached/vented, MRSA/MDRO, tracheobronchitis 5 minutes into infusion via Eclipse (30-minute infusion), patient developed adverse reaction Signs and symptoms Facial and neck flushing, pruritus, swollen lips/tongue, SOB, wheezing, hypoxemia, hypotension

60 Case Study 3 (cont.) Interventions Epinephrine administered via EpiPen 911 called IV diphenhydramine administered O2 administered Rapid administration of IV fluids - 0.9% NS Positioned supine, legs elevated VS monitored Patient transported via ambulance Admitted x 36 hours

61 Reminder

62 Conclusion Anaphylaxis is a potentially life-threatening condition. Anaphylaxis and anaphylactoid reactions produce the same clinical manifestations and are treated exactly the same. Risk factors should be identified in history.

63 Conclusion 3 primary factors that result in need for emergency care: Vasodilation Bronchoconstriction Increased vascular permeability Be prepared for rapid implementation of emergency interventions Any issues with ABC include administration of epinephrine and calling 911

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65 References 1. Benjamini, E., Sunshine G., Leskowitz, S. (1996). Immunology: A Short Course, 3rd ed. New York: Wiley. 2. Beulow, B., Kaliner, M. (2015, Feb 9). Immediate Hypersensitivity Reactions. Medscape. Retrieved from 3. Cheng, A. Emergency treatment of anaphylaxis in infants and children. Pediatr Child Health Jan; 16(1): Frellick M. (2017, Feb. 13). AAP Updates Guidance on Epinephrine Use for Anaphylasix. Medscape. Retrieved from 5. Janeway, CA., Travers, P., Walport, M., et al. (2001). Immunobiology: The Immune System in Health and Disease, 5th edition. New York: Garland Science. 6. Johnson, R., Peebles, R. (2004). Anaphylactic Shock: Pathophysiology, Recognition, and Treatment. Semin Respir Crit Care Med. 25(6), Limmer DD., Mistovich JJ., Krost WS. (2004, June 1). Anaphylactic and Anaphylactoid Reactions. EMS World. Retrieved from 8. Rothenberg, M. (2000). Mechanisms of Disease: Pathophysiology A Plain English Approach. Eau Claire, Wisconsin: PESI Healthcare. 9. Shahzad Mustafa, S., Kaliner M., et al. (2017, Feb 22). Anaphylaxis. Medscape. Retrieved from Tang, A. (2003). A Practical Guide to Anaphylaxis. Am Fam Physician. 68(7),