Anaphylaxis. Dr Lynda Vandertuin

Transcription

1 Dr Lynda Vandertuin 1

2 Anaphylaxis is a clinical emergency = Anaphylaxis is a potentially fatal disorder 2

3 What is the incidence? (minimal data in pediatric population) Anaphylaxis 1 to 4 per 1000 ED visits in adults (UK) increase of 7x in the last 7 years (UK) 1 per 1000 children have personalized anaphylaxis management plan (France) prescription rate of adrenaline 1% of the population (Canada) severe anaphylaxis is fatal in % of cases (USA) 3

4 What is Anaphylaxis? Anaphylaxis Defined as a severe, acute, life-threatening generalized or systemic hypersensitivity reaction! Caused by the systemic release of mediators from mast cells & basophils in response to an allergen! 4

5 How is the clinical diagnosis decided? Several panels of experts meet regularly to define anaphylaxis and its management & treatment : July 2005 : Second symposium on the Definition and Management of Anaphylaxis with clinical criteria April 2007 : Position paper published by the European Academy of Allergology& Clinical Immunology (EAACI) on the management of anaphylaxis in childhood March 2011 : Practice paper published by the World Allergy Organization on Anaphylaxis guidelines 5

6 Definition of Anaphylaxis? Simons et al. WAO Anaphlaxis Guidelines: Summary. March

7 The Critical Criteria for the diagnosis? the notion of acute onset of illness : minutes to several hours! the notion of skin involvement : applicable in 80 to 90% of children (if absent not exclusive) if clinical features are present in patients with a known history of allergy if clinical features are present after exposure to a likely or known allergen 7

8 Different types of immunological responses : Type I : mediated by IgE Type II : mediated by tissue Antibody IgGand IgM Type III : mediated by Immune Complexes Type IV : cell-mediated Immune Complexes 8

9 Pathophysiology of Anaphylaxis : Science & Technology 6th Report. July

10 Pathophysiology of Anaphylaxis : copyright Alila Medical Media 10

11 Principal Mediators implicated : PRIMARY Histamin Serotonin Eosinophil Chemotactic Factor Neutrophil chemotactic factor Proteases SECONDARY Platelet-activating factor Leukotrienes (SRS-A) Prostaglandins Bradykines Cytokines IL-1 and TNF-α IL-2 to IL-6, TGF-β, GM-CSF Effects Increased vascular permeability: smooth-muscle contraction Increased vascular permeability; smooth-muscle contraction Eosinophil chemotaxis Neutrophil chemotaxis Bronchial mucus secretion; degradation of blood-vessel basement membrane; generation of complement split products Effects Platelet aggregation and degranulation; contraction of pulmonary smooth muscles Increased vascular permeability; contraction of pulmonary smooth muscles Vasodilation; contraction of pulmonary smooth muscles; platelet aggregation Increased vascular permeability; smooth-muscle contraction Systemic anaphylaxis; increased expression of CAMs on venular endothelial cells Various effects 11

12 Response based on the site of contact of the allergen : 12

13 Principal Agents incriminated in Anaphylaxis in Children : 56 % Food hypersensitivity 5 % Drug hypersensitivity 5 % Insect hypersensitivity Latex hypersensitivity Bioactive substances eg. blood, plasma Exercise Induced Environmental allergens eg. dust, pollen Idiopathic 13

14 Principal Food Allergens : peanuts and other nuts sesame seed fish shell fish milk eggs wheat, buckwheat soya celery, spices additives (vs intolerance) Moneret-Vautrin et al. Allergy

15 Principal Drug Allergens : antimicrobial p.ex. Intramuscular penicillin, antituberculosis antiviral antifungal NSAIDS βeta-blockers chemotherapeutic agents p.ex. Carboplatin, doxorubicin biological agents p.ex. Monoclonal antibodies : cetuximab, rituximab, infliximab& omalizumab contaminants in medications p.ex. Sulfate in heparin Herbal formulations Radio-contrast media (RCM) Peri-operative interventions : neuromuscular blocking agents, hypnotics, opioids Allergen-specific immunotherapy Vaccins (rarely) 15

16 Principal Insect Allergens : Hymenoptera venin : honeybee, bumblebee, wasp, hornet Diptera : mosquito Acarina : ticks Anaphylaxis may occur even after the first sting 16

17 Principal Drug Allergens : Moneret-Vautrin et al. Allergy

18 Signs and Symptoms of anaphylaxis : 18

19 Signs and Symptoms of anaphylaxis : Cutaneous manifestations urticaria, pruritus, angioedema, flushing In Children 80-90% 19

20 Signs and Symptoms of anaphylaxis : Respiratory Upper Airway (UA) : stridor, hoarseness, laryngeal edema, uvular edema, swollen lips/tongue, sneezing, rhinorrhea Lower airway (LA) : coughing, dyspnea, bronchospasm, tachypnea, respiratory arrest In Children 60-70% 20

21 Signs and Symptoms of anaphylaxis : Cardiovascular tachycardia, hypotension, syncope, arrhythmias, pallor, cyanosis, cardiac arrest In Children 10 30% 21

22 Signs and Symptoms of anaphylaxis : Gastrointestinal nausea, vomiting, diarrhea, abdominal pain In Children < 10% 22

23 Signs and Symptoms of anaphylaxis : General/CNS fussiness, irritability, drowsiness, lethargy, unconsciousness, somnolence 23

24 Signs and Symptoms of anaphylaxis : Moneret-Vautrin et al. Allergy

25 Anaphylaxis is a trigger of multiple systems : 25

26 Stages of Anaphylaxis (according to Muller) : Stage Skin Digestive Respiratory Cardiovascular I Generalized hives &iitching Neurological Ø Ø Ø Change in activity level II I + Angioedema Abdominal pain, diarrhoea, vomiting III II II + Dysphagia IV II III + loss of bowel control Ø Ø Anxiety, vertigo Dyspnoea, hoarseness, stridor, moderate wheezing III + cyanosis, saturation < 92%, respiratory arrest Ø Hypotension, dysrhythmia, bradycardia, cardiac arrest Light headedness, feeling of pending doom Confusion, loss of consciousness 26

27 Plan for Patient Management : 1. First Aid treatment in the community 2. Hospital management 27

28 First Aid treatment to be used in the community : Self-injectableintramuscular (IM) epinephrine Available in 2 doses : 0.15mg (Junior) & 0.3mg In children recommended epinephrine (1:1000) dose of 0.01mg/kg : Epipen/JextJunior is applicable for children 10 to 30 kg 28

29 Correct use of self-injectable Epinephrine : 29

30 Correct use of self-injectable Epinephrine : 30

31 First Aid treatment in the community : Whether epinephrine is given or not URGENTLY seek medical care at the nearest ED 31

32 Acute management of anaphylaxis in Hospital (1) : 1. Rapid and thorough assessment of airway, breathing and circulation 2. Immediate and concurrent administration of IM epinephrine 3. If signs of Upper Airway Obstruction (stridor, swollen tongue or uvular edema) OR severe respiratory distress early preparation of airway management is critical : rapid sequence intubation 4. Establish intravenous IV access, without delaying administration of epinephrine 5. Supplemental oxygen delivery & full cardiorespiratory monitoring 32

33 Acute management of anaphylaxis in Hospital (2) : 6. Increased vascular permeability with potential loss of 35% of circulating blood loss volume : 2 large IV lines 7. Aggressive fluid resuscitation with 20 ml/kg bolus of normal saline if cardiovascular involvement and repeated as necessary 8. Intraosseous needle (IO) should be placed if IV access is non obtained 9. Continuous reassessment of vital signs & management to determine need for intubation, more fluids or perhaps inotropic support 33

34 Acute management of anaphylaxis in Hospital (3) : 10. Initiate second-line pharmacologic therapy : H1 and H2- histamin antagonists and Steroids 11. Consider the need for inhaled medications such as nebulized epinephrine (in the case of UAO) or salbutamol (in the case of LAO p.ex. wheezing or dyspnea) 12. Continuously reassess the patient 34

35 Epinephrine (Adrenaline) : First-Line treatment Essential medication for the treatment of anaphylaxis 35

36 Effects of Epinephrine : Anaphylaxis Life-saving due to its alpha-1 adrenergic vasoconstrictor effects in most body organ systems : Ability to prevent and relieve airway obstruction due to mucosal edema. Prevent and relieve hypotension and shock. Beta-1 adrenergic agonist inotropic and chronotropic properties : increase force and rate of cardiac contractions. Beta-2 adrenergic agonist properties : decrease mediator release, bronchodilatation& relief of urticaria 36

37 Effects of Epinephrine : Anaphylaxis Epinephrine Alpha-1 adrenergic Alpha-2 adrenergic Beta-1 adrenergic Beta-2 adrenergic vasoconstriction Nor release Inotrope Bronchodilation peripheral VR Insulin release Chronotrope Vasodilation mucosal edema Glycogenolysis Mediator release Kemp et al. Allergy

38 Epinephrine (Adrenaline) : IM administration 0.01mg/kg of a 1:1000 (1mg/mL) solution Dose 0.3 mg in children > 30 kg ; 0.15 mg children 10 to 30 kg Peak plasma and tissue concentrations are achieved rapidly Repeat the dose every 5-15 minutes according to the severity of the episode and the initial response Response achieved after 1 to 2 doses Biphasic response within 1 to 72 hours (usually within 8 to 10 hours) 38

39 Epinephrine (Adrenaline) : Biphasic response Ellis et al. CMAJ,

40 Epinephrine (Adrenaline) : Adverse Effects Pallor, tremor, anxiety, palpitations, dizziness and headache When present indicates therapeutic dose was given Serious AE : ventricular arrhythmias, hypertensive crisis and pulmonary edema-> indicate an overdose treatment or rapid IV treatment or bolus administration, dosing error (1:1000 solution given as dose IV p.ex 0.1mg/kg of 1:10 000) 40

41 Epinephrine (Adrenaline) : therapeutic window Kemp et al. Allergy

42 Acute management of anaphylaxis in Hospital : Several algorithms for patient management are proposed 1. European Academy of Allergology and clinical immunology (EAACI) taskforce on Anaphylaxis in Children 42

43 What is the mechanism of Anaphylaxis : 43

44 Acute management of anaphylaxis in Hospital : Several algorithms for patient management are proposed 2. Canadian Paediatric Society : Acute Care Committee 44

45 Acute management of anaphylaxis in Hospital 45

46 Differential Diagnosis in Anaphylaxis : Shock of other origin septic, hemorrhagic, cardiogenic : no mucocutaneous signs to support diagnosis of anaphylaxis Acute asthma : not associated with urticaria, angioedema, abdominal pain and hypotension Syncope : hypotension but also pallor and sweating Anxiety/panic attacks : sense of impending doom, breathlessness, flushing, tachycardia and gastrointestinal symptoms but not urticaria, wheezing and hypotension Postprandial syndromes, Excess endogenous histamine syndromes, Flush syndromes, Nonorganic diseases Age- and sex-related differential diagnosis such as choking and aspiration of a nut or other foreign body in infants 46

47 Differential Diagnosis in Anaphylaxis : WHO Pediatric Handbook 47

48 Laboratory Tests in Anaphylaxis : No initial testing is required as this is a life-threatening emergency! However, prepare one extra tube of blood Tryptase blood level : 15 minutes to 3 hours after symptom onset -may be elevated in anaphylaxis triggered by insect stings or injected medication - normal after anaphylaxis if triggered by food and in normotensive patients - serial measures considered more useful Histamine blood level : 15 to 60 minutes after symptom onset Medication blood levels and/or toxic neuropathies (medications or toxins as in insecticide ingestion) Other blood tests in experimentation : PAF and carboxypeptidase A3 48

49 Second-Line Medications in Anaphylaxis : Should never delay the prompt administration of Epinephrine Evidence Based Use and Effect extrapolated from use in treatment of other diseases 49

50 Second-Line Medications in Anaphylaxis : H1-Antihistamines : relieve itching, flushing, urticaria, angioedema and nasal and eye symptoms Beta-2 Adrenergic Agonists: additional treatment for coughing, wheezing and shortness of breath (LAO) not relieved by epinephrine Glucocorticoids: switch off transcription of activated genes for proinflammtoryproteins & potentially relieve protracted anaphylaxis symptoms and prevent biphasic anaphylaxis H2-Antihistamines: decrease flushing, headache and other symptoms, may increase hypotension 50

51 Second-Line Medications in Anaphylaxis : H1- antihistamines Chlorpheniramin (iv/im) Clemastine (iv) Diphenhydramin (oral) Cetrizine/Levocetrizine (oral) Loratadine/Desloratadine (oral) Beta-2 Adrenergic Agonists Salbutamol (aerosol/meterdosed/iv) Glucocorticoids Hydrocortisone (oral) Methylprednisolone (iv) Prednisone/solone (oral) H2 - antihistamines Cimetidine (iv/oral) 5-10mg 0.1mg/kg (max 4mg) mg/kg (max 1mg) 1-2mg/kg (max mg) 0.2mg/kg 10mg (> 12 years) Drops by age/100mcg puff/ 5-10mcg/kg/min 0.5-2mg/kg (max 50mg) 2mg/kg (max 100mg) 2mg/kg (max 60mg) 51

52 Outcome of Severe Anaphylaxis : Fatal : 0.65 to 2% of cases Age : 2 to 3 years of age Presentation : Acute severe bronchospasm in 96% Agent : peanuts 63% & other tree nuts 31% 52

53 Patient factors that increase the risk of severe or fatal anaphylaxis : patients who have had a previous anaphylactic reaction and severe previous reactions very young & very old age concomitant diseases : asthma, cardiovascular diseases, mast cell disorders (mastocytosis or clonal mast cell disorders) concurrent medications : β-adrenergic blockers & ACE-inhibitors non-prescription or recreational drugs, ethanol Cofactors that might amplify an acute episode : exercise, intercurrent infections 53

54 Hospital monitoring : Anaphylaxis Biphasic anaphylaxis occurs in up to 11% of children If moderate respiratory or cardiovascular compromise : minimum 4 hours surveillance Patients with severe or protracted anaphylaxis : minimum 8 hours surveillance 54

55 Discharge management : Identification of the allergen : detailed history of the acute episode recognize if history of Mastocytosis, C1 inhibiteur deficit Instruction in self-treatment by prescription of epinephrine auto-injectors & explanation of use : why, when, and how! Personalized written anaphylaxis emergency action plan Medical identification (bracelet or wallet card) Organize follow-up with an allergy/immunology specialist : confirmation of the specific anaphylaxis trigger(s), trigger avoidance and if possible, immunomodulation 55

56 Indications for prescribing self-injectable epinephrine : Previous CV or respiratory reaction to a food, insect sting or latex Exercise induced anaphylaxis Idiopathic anaphylaxis Child with food allergy and co-existent persistent asthma Any reaction to small amounts of a food History of mild reaction to peanut or tree nut Remoteness of medical facility Food allergic reaction in teenagers 56

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58 Job Aid Summary (GSK) : 58

59 Job Aid Summary (GSK) : 59

60 Job Aid Summary (GSK) : 60

61 Job Aid Summary (GSK) : 61

62 Job Aid Summary (GSK) : 62

63 Job Aid Summary (GSK) : 63

64 Job Aid Summary (GSK) : 64

65 Job Aid Summary (GSK) : 65

66 Thank you for your attention! Any Questions? 66

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68 References : 1. Simons et al. World Allergy Organization anaphylaxis guidelines : Summary. J Allergy ClinImmunolvol127, no 3. March Muraroet al. The management of anaphylaxis in childhood: position paper of the EAACI. Allergy Cheng A. Emergency treatment of anaphylaxis in infants and children. Paediatr Child Health 2011: 16 (1); Kemp et al. Epinephrine : the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy 2008: 63; Stone et al. Mediators Released during Human Anaphylaxis. Curr Allergy Asthma Rep Nov Ellis et al. Diagnosis and Management of Anaphylaxis. CMAJ 2003: 169 (4). 7. Moneret-Vautrin et al. Epidemiology of life-threatening and lethal anaphylaxis: a review. Allergy 2005: 60;

69 Question QCM no. 1 Sara 8 years of age immediately after eating a shrimp cocktail felt her face become swollen, with urticariaon her face and chest. She complained of abdominal pain and had vomiting. What is her diagnosis? A. Allergy to shrimp B. Allergy to all fish and shell fish C. Test again later by having her eat a piece of shrimp D. Sara had a minor stage I reaction and can eat as much shrimp as she likes 69

70 Question QCM no. 1 Sara 8 years of age immediately after eating a shrimp cocktail felt her face become swollen, with urticariaon her face and chest. She complained of abdominal pain and had vomiting. What is her diagnosis? A. Allergy to shrimp B. Allergy to all fish and shell fish C. Test again later by having her eat a piece of shrimp D. Sara had a minor stage I reaction and can eat as much shrimp as she likes 70

71 Question QCM no. 2 Max, 3 years of age, was eating a kebab for the first time. Rapidly after he finished the kebab, he showed signs of respiratory distress with wheezing and his lips became swollen and he vomited once. Which treatment should he receive? A. Oral anti-histamine and nebulized Salbutamol B. Oral anti-histamine and oral prednisone C. IM Epinephrine D. IM Epinephrine, anti-histamine and glucocortoids 71

72 Question QCM no. 2 Max, 3 years of age, was eating a kebab for the first time. Rapidly after he finished the kebab, he showed signs of respiratory distress with wheezing and his lips became swollen and he vomited once. Which treatment should he receive? A. Oral anti-histamine and nebulized Salbutamol B. Oral anti-histamine and oral prednisone C. IM Epinephrine D. IM Epinephrine, anti-histamine and glucocortoids 72

73 Question QCM no. 3 Hugo 5 years of age, was playing in the park, when suddenly he is stung on the right arm by a bumblebee. His arm begins to swell over the next 20 minutes and he feels very lethargic. His mother brings him to the emergency where is BP is measured at 60/30 mmhg with tachycardia at 160/min. His peripheral perfusion is poor. What is the diagnosis? A. Hugo is afraid of bees and suffered a syncope after he saw the bee B. Anaphylaxis shock (stage IV) and immediate IM Epinephrine should be given C. Syncope and local allergic reaction stage I and he should receive oral anti-histamines D. None of the above 73

74 Question QCM no. 3 Hugo 5 years of age, was playing in the park, when suddenly he is stung on the right arm by a bumblebee. His arm begins to swell over the next 20 minutes and he feels very lethargic. His mother brings him to the emergency where is BP is measured at 60/30 mmhg with tachycardia at 160/min. His peripheral perfusion is poor. What is the diagnosis? A. Hugo is afraid of bees and suffered a syncope after he saw the bee B. Anaphylaxis shock (stage IV) and immediate IM Epinephrine should be given C. Syncope and local allergic reaction stage I and he should receive oral anti-histamines D. None of the above 74

75 Question QCM no. 4 By what mechanism does Epinephrine (Adrenaline) function to improve the signs of anaphylaxis? A. Alpha-1 receptor : increases peripheral vascular resistance B. Beta-1 adrenergic receptor : increases chronotropy C. Beta-2 adrenergic receptor : increases bronchodilatation D. All of the above 75

76 Question QCM no. 4 By what mechanism does Epinephrine (Adrenaline) function to improve the signs of anaphylaxis? A. Alpha-1 receptor : increases peripheral vascular resistance B. Beta-1 adrenergic receptor : increases chronotropy C. Beta-2 adrenergic receptor : increases bronchodilatation D. All of the above 76

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78 Allergens may cause different responses based on the immunological mechanism : 78