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The AA Talk : Anaphylaxis and Angioedema: an update Professor Anthony F T Brown Department of Emergency Medicine Royal Brisbane and Women’s Hospital
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COI Disclosure: Autumn Symposium 2016 Presenter: Professor Anthony F T Brown Educational / research funding (present*/past + ): ~ Boehringer Ingelheim* ~ Shire [ manufacturer of icatibant ]* ~ Avant* ~ Bayer* ~ Roche + Board Membership: ~ Traumalink* ~ EMF / QEMRF +
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Anaphylaxis and Angioedema: an update Aims Aetiology / ‘summation anaphylaxis’ Aetiology / ‘summation anaphylaxis’ Cardiac ischaemia Cardiac ischaemia primary / secondary – adrenaline use / misuse / non-use primary / secondary – adrenaline use / misuse / non-use Angioedema Angioedema non-histaminergic non-histaminergic HAE / ACE-I HAE / ACE-I
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Eminence base for Anaphylaxis PubMed Anaphylaxis – a practice parameter update 2015Anaphylaxis – a practice parameter update 2015 Ann Allergy Asthma Immunol 2015;115:341-384 Ann Allergy Asthma Immunol 2015;115:341-384 Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology: Allergy 2014;69:1026-45Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology: Allergy 2014;69:1026-45 Emergency department diagnosis and treatment of anaphylaxis: a practice parameter: Ann Allergy Asthma Immunol 2014;113:599-608Emergency department diagnosis and treatment of anaphylaxis: a practice parameter: Ann Allergy Asthma Immunol 2014;113:599-608
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Anaphylaxis Preformed mediators (histamine / tryptase/ chymase / ECF) Preformed mediators (histamine / tryptase/ chymase / ECF) Newly formed mediators (leukotrienes / TNF-α / PAF) Newly formed mediators (leukotrienes / TNF-α / PAF) Actions: vasodilation; capil permeability; bronchoconstriction; glandular secretion; chemotaxis; I o cardiac effect glandular secretion; chemotaxis; I o cardiac effect Aetiology / mediator function
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Anaphylaxis Aetiology / ‘Summation anaphylaxis‘ Co-morbidities: Asthma Asthma Intercurrent infection Intercurrent infection Alcohol Alcohol Beta blockers / NSAIDs Beta blockers / NSAIDs / ACEIs / ACEIs Premenstrual status Premenstrual status Exercise / Food Exercise / Food ‘Stress’ ‘Stress’
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Anaphylaxis Preformed mediators (histamine / tryptase/ chymase / ECF) Preformed mediators (histamine / tryptase/ chymase / ECF) Newly formed mediators (leukotrienes / TNF-α / PAF) Newly formed mediators (leukotrienes / TNF-α / PAF) Actions: vasodilation; capil permeability; bronchoconstriction; glandular secretion; chemotaxis; I o cardiac effect glandular secretion; chemotaxis; I o cardiac effect Aetiology / mediator function
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Anaphylaxis Cardiac mast cells Cardiac mast cells direct mediator effect direct mediator effect coronary artery vasoconstriction coronary artery vasoconstriction ‘Kounis syndrome’ ‘Kounis syndrome’ I o Cardiac effect / ischaemia
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Anaphylaxis Cardiac mast cells Cardiac mast cells direct mediator effect direct mediator effect coronary artery vasoconstriction coronary artery vasoconstriction ‘Kounis syndrome’ ‘Kounis syndrome’ Known or subclinical coronary artery disease Known or subclinical coronary artery disease hypotension / hypoxia trigger +/- plaque rupture hypotension / hypoxia trigger +/- plaque rupture 2 o Cardiac effect / ischaemia
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Anaphylaxis Cardiac mast cells Cardiac mast cells direct mediator effect direct mediator effect coronary artery vasoconstriction coronary artery vasoconstriction ‘Kounis syndrome’ ‘Kounis syndrome’ Known or subclinical coronary artery disease Known or subclinical coronary artery disease hypotension / hypoxia trigger +/- plaque rupture hypotension / hypoxia trigger +/- plaque rupture Adrenaline effect Adrenaline effect hypertension / tachyarrhythmia / ↑ myocardial O 2 demand hypertension / tachyarrhythmia / ↑ myocardial O 2 demand coronary vasospasm coronary vasospasm ↑ platelet aggregation ↑ platelet aggregation Simons E. J All Clin Immunol 2011;127:593.e1-e22 Simons E. J All Clin Immunol 2011;127:593.e1-e22 2 o Cardiac effect / ischaemia
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Management: First-line therapy ADRENALINE IM early (not sc) ADRENALINE IM early (not sc) Airway swelling, wheeze, dyspnoea, Airway swelling, wheeze, dyspnoea, Tachycardia, hypotension, LOC Tachycardia, hypotension, LOC 1:1000 (1 mL amp) 1:1000 (1 mL amp) 0.01 mg/kg up to 0.5 mg = (0.3 -) 0.5 mL 0.01 mg/kg up to 0.5 mg = (0.3 -) 0.5 mL Adjust dose for age / body mass / known or suspected IHD Adjust dose for age / body mass / known or suspected IHD Upper, outer thigh Upper, outer thigh May be repeated every 5 min May be repeated every 5 min (Pre-) / In-Hospital Adrenaline (Pre-) / In-Hospital
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Management: First-line therapy ADRENALINE IM early Adjust dose for age / body mass / known or suspected IHD (Pre-) or In-Hospital Adrenaline (Pre-) or In-Hospital 58 yr male 1 mg adrenaline IMI
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Management: First-line therapy ADRENALINE IM early Adjust dose for age / body mass / known or suspected IHD (Pre-) or In-Hospital Adrenaline (Pre-) or In-Hospital ECG 10 mins later: prox LAD occlusion
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Anaphylaxis Management Adrenaline IV cautiously Airway compromised Airway compromised Critical wheeze Critical wheeze Critical hypotension Critical hypotension Unresponsive … Unresponsive … Must be monitored Must be monitored ECG and SpO 2 ECG and SpO 2 Critical, deteriorating anaphylaxis… Critical, deteriorating anaphylaxis…
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Anaphylaxis Management Adrenaline IV Adrenaline IV 1:100 000 dilution / 10 g per mL 1:100 000 dilution / 10 g per mL 0.75 -1.5 g/kg initially 0.75 -1.5 g/kg initially ≡ 50 – 100 g initially over 5 - 10 min ≡ 50 – 100 g initially over 5 - 10 min or by infusion: 1 mL (1 mg) of 1:1000 in 100 mL or by infusion: 1 mL (1 mg) of 1:1000 in 100 mL N.saline at 30 – 100 mL/hr (ie. 5 - 15 g / min) N.saline at 30 – 100 mL/hr (ie. 5 - 15 g / min) Critical anaphylaxis
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Fatal anaphylaxis Adrenaline Underused Underused No adrenaline given prior to cardiac arrest – 14% No adrenaline given prior to cardiac arrest – 14% No adrenaline given at all – 38% No adrenaline given at all – 38% Pumphrey R. Clin Exp All 2000;30:1144-50
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Fatal anaphylaxis Underused Underused No adrenaline given prior to cardiac arrest – 14% No adrenaline given prior to cardiac arrest – 14% No adrenaline given at all – 38% Pumphrey R. Clin Exp All 2000;30:1144-50 No adrenaline given at all – 38% Pumphrey R. Clin Exp All 2000;30:1144-50 Severe asthma: ↑ risk – esp. food allergy Severe asthma: ↑ risk – esp. food allergy CVS disease: ↑ risk – esp. in elderly CVS disease: ↑ risk – esp. in elderly Mastocytosis: ↑ risk – esp. Hymenoptera sting-induced Mastocytosis: ↑ risk – esp. Hymenoptera sting-induced Simons F. Int Arch All Immunol 2013;162:193-204 Simons F. Int Arch All Immunol 2013;162:193-204
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Anaphylaxis Observation ED observation (> 95 % all patients) ED observation (> 95 % all patients) 4 – 6 hours 4 – 6 hours risk of biphasic reaction < 1- 5% risk of biphasic reaction < 1- 5% (Douglas D. J Allergy Clin Immunol 1994; 93: 977-85) (Douglas D. J Allergy Clin Immunol 1994; 93: 977-85) 8 – 10 hours: asthmatics / elderly / food allergen 8 – 10 hours: asthmatics / elderly / food allergen
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Angioedema Bradykinin mediated Bradykinin mediated Absence of urticaria / pruritus Absence of urticaria / pruritus +/- abdo pain present +/- abdo pain present Hereditary angioedema (HAE) Hereditary angioedema (HAE) C1 esterase inhibitor deficiency (C1-INH) C1 esterase inhibitor deficiency (C1-INH) autosomal dominant autosomal dominant starts in adolescence starts in adolescence Low C4 complement levels (screen) Low C4 complement levels (screen) Non-histaminergic
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Angioedema Bradykinin mediated Bradykinin mediated Absence of urticaria / pruritus Absence of urticaria / pruritus +/- abdo pain present +/- abdo pain present Hereditary angioedema (HAE) Hereditary angioedema (HAE) C1 esterase inhibitor deficiency (C1-INH) C1 esterase inhibitor deficiency (C1-INH) autosomal dominant autosomal dominant starts in adolescence starts in adolescence Low C4 complement levels (screen) Low C4 complement levels (screen) Treatment HAE Treatment HAE C1-INH concentrate : Berinert 20 units/kg IV or Cinryze 1000 units IV C1-INH concentrate : Berinert 20 units/kg IV or Cinryze 1000 units IV Bradykinin-2 receptor blocker : icatibant (Firazyr) 30 mg SC Bradykinin-2 receptor blocker : icatibant (Firazyr) 30 mg SC Non-histaminergic
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Angioedema Bradykinin mediated Bradykinin mediated Absence of urticaria / pruritus Absence of urticaria / pruritus +/- abdo pain present +/- abdo pain present Hereditary angioedema (HAE) Hereditary angioedema (HAE) C1 esterase inhibitor deficiency (C1-INH) C1 esterase inhibitor deficiency (C1-INH) autosomal dominant autosomal dominant starts in adolescence starts in adolescence Low C4 complement levels (screen) Low C4 complement levels (screen) ACEI-induced ACEI-induced Much, much more common … Much, much more common … Non-histaminergic
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Angioedema Bradykinin mediated Bradykinin mediated Absence of urticaria / pruritus Absence of urticaria / pruritus +/- abdo pain present +/- abdo pain present Hereditary angioedema (HAE) Hereditary angioedema (HAE) C1 esterase inhibitor deficiency (C1-INH) C1 esterase inhibitor deficiency (C1-INH) autosomal dominant autosomal dominant starts in adolescence starts in adolescence Low C4 complement levels (screen) Low C4 complement levels (screen) ACEI-induced ACEI-induced Much, much more common … Much, much more common … still try adrenaline still try adrenaline Non-histaminergic
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Angioedema Bradykinin mediated Bradykinin mediated Absence of urticaria / pruritus Absence of urticaria / pruritus +/- abdo pain present +/- abdo pain present Hereditary angioedema (HAE) Hereditary angioedema (HAE) C1 esterase inhibitor deficiency (C1-INH) C1 esterase inhibitor deficiency (C1-INH) autosomal dominant autosomal dominant starts in adolescence starts in adolescence Low C4 complement levels (screen) Low C4 complement levels (screen) ACEI-induced ACEI-induced Much, much more common … Much, much more common … still try adrenaline still try adrenaline icatibant (Firazyr) 30 mg SC ? (OFF LABEL) icatibant (Firazyr) 30 mg SC ? (OFF LABEL) Non-histaminergic
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Angioedema Bradykinin mediated Bradykinin mediated Absence of urticaria / pruritus Absence of urticaria / pruritus +/- abdo pain present +/- abdo pain present Hereditary angioedema (HAE) Hereditary angioedema (HAE) C1 esterase inhibitor deficiency (C1-INH) C1 esterase inhibitor deficiency (C1-INH) autosomal dominant autosomal dominant starts in adolescence starts in adolescence Low C4 complement levels (screen) Low C4 complement levels (screen) ACEI-induced ACEI-induced Much, much more common Much, much more common still try adrenaline … still try adrenaline … icatibant (Firazyr) 30 mg SC ? (OFF LABEL) icatibant (Firazyr) 30 mg SC ? (OFF LABEL) Non-histaminergic
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Angioedema Bradykinin mediated Bradykinin mediated Absence of urticaria / pruritus Absence of urticaria / pruritus +/- abdo pain present +/- abdo pain present Hereditary angioedema (HAE) Hereditary angioedema (HAE) C1 esterase inhibitor deficiency (C1-INH) C1 esterase inhibitor deficiency (C1-INH) autosomal dominant autosomal dominant starts in adolescence starts in adolescence Low C4 complement levels (screen) Low C4 complement levels (screen) ACEI-induced ACEI-induced Much, much more common Much, much more common still try adrenaline … still try adrenaline … icatibant (Firazyr) 30 mg SC ? (OFF LABEL) icatibant (Firazyr) 30 mg SC ? (OFF LABEL) Non-histaminergic X
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Anaphylaxis and Angioedema: an update Conclusions ‘Summation anaphylaxis’ – beware asthma / elderly ‘Summation anaphylaxis’ – beware asthma / elderly Cardiac ischaemia Cardiac ischaemia primary effect / secondary to adrenaline use + misuse primary effect / secondary to adrenaline use + misuse Angioedema Angioedema non-histaminergic non-histaminergic HAE / ACE-I – watch airway risk / know your drugs HAE / ACE-I – watch airway risk / know your drugs
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Anaphylaxis and Angioedema: an update Conclusions Be prepared … Be prepared … Never underestimate … Never underestimate …
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Anaphylaxis and Angioedema: an update QUESTIONS QUESTIONS
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19 yr female presents with long history of recurrent abdo pain, hand and foot swelling, and lip swelling. Her uncle died after a visit to the Dentist. Which answer best fits this history? a). Don’t know, but I’d get a pelvic ultrasound and admit GA b). Don’t know, but I would advise her to avoid the Dentist c). No connection between these events: refer back to the GP d). Hereditary angioedema e). Food allergy – take a dietary history: refer back to the GP f). ‘Abdominal migraine’ – or malingering : refer back to the GP
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19 yr female presents with long history of recurrent abdo pain, hand and foot swelling, and lip swelling. Her uncle died after a visit to the Dentist. Answer a). Don’t know, but I’d get a pelvic ultrasound and admit GA b). Don’t know, but I would advise her to avoid the Dentist c). No connection between these events: refer back to the GP d). Hereditary angioedema e). Food allergy – take a dietary history: refer back to the GP f). ‘Abdominal migraine’ – or malingering : refer back to the GP
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You believe you have diagnosed a new case of HAE in this 19 yr female. You decide to send some diagnostic tests from ED Which answer best fits this plan? a). FBC / ELFTs / Lipase / MSU / bHCG i. e. “ the usual ” b). Chromosome mapping – loci on c.11 c). C4 level; if low – C1 INH level d). C4 level; if low – C1 INH level + C1 INH function e). C4 level; if low – C1 INH level + C1 INH function, with results to also go to the GP (add his / her name to Path form) to also go to the GP (add his / her name to Path form)
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You believe you have diagnosed a new case of HAE in this 19 yr female. You decide to send some diagnostic tests from ED Answer a). FBC / ELFTs / Lipase / MSU / bHCG i.e. “ the usual ” b). Chromosome mapping – loci on c.11 c). C4 level; if low – C1 INH level d). C4 level; if low – C1 INH level + C1 INH function e). C4 level; if low – C1 INH level + C1 INH function, with results to also go to the GP (add his / her name to Path form) to also go to the GP (add his / her name to Path form)
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Six months later the same female, now aged 20 yr, returns and asks for you in person. She did indeed have HAE, thinks you are amazing, but has marked lip and tongue swelling + right hand pain. Which answer best fits what you do next ? a). You agree you are an awesome doctor, and ask her to write a letter of thanks to the Director a letter of thanks to the Director b). You tell her to go get an ASCIA HAE Action Plan card and carry it with her at all times carry it with her at all times c). Move her to Resus / get the consultant involved – and still ask for a letter of thanks to the Director ask for a letter of thanks to the Director d). Move her to Resus / get the consultant involved – and decide to give some CI INH iv decide to give some CI INH iv e). C4 level; if low – C1INH level + C1INH function, with results to also go to the GP (add his / her name to Path form) to also go to the GP (add his / her name to Path form)
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Six months later the same female, now aged 20 yr, returns and asks for you in person. She did indeed have HAE, thinks you are amazing, but has marked lip and tongue swelling + right hand pain. Answer a). You agree you are an awesome doctor, and ask her to write a letter of thanks to the Director a letter of thanks to the Director b). You tell her to go get an ASCIA HAE Action Plan card and carry it with her at all times carry it with her at all times c). Move her to Resus / get the consultant involved – and still ask for a letter of thanks to the Director ask for a letter of thanks to the Director d). Move her to Resus / get the consultant involved – and decide to give some CI INH iv decide to give some CI INH iv e). C4 level; if low – C1INH level + C1INH function, with results to also go to the GP (add his / her name to Path form) to also go to the GP (add his / her name to Path form)
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CI INH iv (Berinert ® ) dose is 20 units/kg iv. You agree with the Consultant it is indicated, and want to write it up. Which answer best fits what may happen next ? a). Berinert ® is TGA approved / on LAM / not on Imprest / needs ED physician to prescribe / and a call to Pharmacy b). Berinert ® is TGA approved / on LAM / not on Imprest / needs Med Super approval or Immunol / call to Pharmacy etc c). No idea what you are on about – I’ll just write it up d). No idea what you are on about – I’ll just write it up, tell the consultant and let him / her worry about it e). Change your mind and send her home – all too difficult
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CI INH iv (Berinert ® ) dose is 20 units/kg. You agree with the Consultant it is indicated, and want to write it up. Answer a). Berinert ® is TGA approved / on LAM / not on Imprest / needs ED physician to prescribe / and a call to Pharmacy b). Berinert ® is TGA approved / on LAM / not on Imprest / needs Med Super approval or Immunol / call to Pharmacy etc c). No idea what you are on about – I’ll just write it up d). No idea what you are on about – I’ll just write it up, tell the consultant and let him / her worry about it e). Change your mind and send her home – all too difficult
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