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Slide 1 04/18/23
GLORIA™ is supported by unrestricted educational grants from
Slide 2 04/18/23
GLORIA Module 3Allergic Emergencies
Slide 3 04/18/23
Allergic Emergencies
WAO Expert Panel
Authors:Richard F Lockey, USAConnie H Katelaris, AustraliaMichael Kaliner, USA
Contributors:F.Estelle R. Simons, CanadaDaniel Vervloet, France
Slide 4 04/18/23
Allergic Emergencies
Section 1: Anaphylaxis
Section 2: Upper Airway Oedema
Section 3: Severe Asthma Exacerbations
Slide 5 04/18/23
Allergic Emergencies
Section 1: Anaphylaxis
Slide 6 04/18/23
Anaphylaxis Lecture Objectives
After this lecture, participants will:
Have knowledge of the different mechanisms which cause anaphylaxis and the agents which are most likely to cause it;
Be able to recognize the signs and symptoms of anaphylaxis;
Understand how to treat anaphylaxis.
Slide 7 04/18/23
Definition of Anaphylaxis
Anaphylaxis – a syndrome with varied mechanisms, clinical presentations, and severity.
An acute life-threatening reaction.
Usually mediated by an immunologic mechanism, allergic anaphylaxis, but not always.
Includes non-allergic anaphylaxis (formerly referred to as an anaphylactoid reaction).
Results from the release of mast-basophil mediators.
WAO Nomenclature Review Committee JACI 2004
Slide 8 04/18/23
Gell and Coombs’ Hypersensitivity (immunopathologic reactions)
Type I Immediate Type II Cytotoxic Type III Immune Complex Type IV Delayed Hypersensitivity
Types I, II and III can result in immunologically-induced or allergic anaphylaxis
Kemp and Lockey JACI 2002
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Biochemical Mediators and Chemotactic Substances
Degranulation of mast cells and basophils. Preformed granule-associated substances, e.g.,
histamine, tryptase, chymase, heparin, histamine-releasing factor, other cytokines.
Newly generated lipid-derived mediators, e.g., prostaglandin D2, leukotriene B4, PAF, LTC4, LTD4, and LTE4.
Eosinophils may play pro-inflammatory role (release of cytotoxic granule-associated proteins) or anti-inflammatory role (e.g., metabolism of vasoactive mediators).
Kemp and Lockey JACI 2002
Slide 11 04/18/23
Shock Organs in Anaphylaxis
Guinea pig – bronchial smooth muscle constriction. Rabbit – fatal pulmonary artery vasoconstriction
with right ventricular failure. Dog – venous system of liver contracts producing
hepatic congestion. Human – shock organs are the cardiovascular
system, respiratory tract, skin, and gastrointestinal tract. Laryngeal oedema, respiratory failure, and circulatory collapse are common.
Asthma is an important risk factor for death from anaphylaxis.
Kemp and Lockey JACI
2002 Bock, Munoz-Furlong, Sampson JACI 2001
Slide 12 04/18/23
Incidence Analysis of published studies of most common causes 3.3 to 4 million Americans at risk. 1,433 to 1,503 at risk for fatal reaction. Neugut, Ghatak, Miller Arch Int Med 2001
Incidence Based on Epinephrine Rx for Out-of-Hospital Use From Canada and Wales. 0.95% of population in Manitoba, Canada. 0.2 per 1000 in Wales. Incidence increased in Wales between 1994 & 1999.
Simons, Peterson, Black JACI 2002
Rangaraj, Tuthill, Burr, Alfaham JACI 2002
Slide 13 04/18/23
Incidence of Anaphylaxis to Specific Agents 1Antibiotics Most common cause of drug induced anaphylaxis.
Latex Increased incidence last decade. Population at risk includes multiple mucosal exposure to latex (catheterization & surgery) and healthcare workers.
Radiocontrast agents Introduction of lower osmolarity agents reduced reaction rate
Lieberman In: Allergy: Principles and Practice. Mosby, 2003
Slide 14 04/18/23
Incidence of Anaphylaxis to Specific Agents 2
Hymenoptera stings Incidence ranges from 0.4% to 5% Estimated fatalities 100 per year in U.S.A.
Food Estimated 2% of US population has food allergies with up to 100 deaths per year Shellfish most common in adults; peanuts in children
Lieberman In Allergy: Principles and Practice Mosby, 2003
Slide 15 04/18/23
Incidence of Anaphylaxis to Specific Agents 3
Perioperative anaphylaxis Incidence ranges from 1 in 4500 to 1 in 2500 cases of general anaesthesia
Mortality rate can be as high as 3.4%
Most common agents responsible are muscle relaxants, which account for 50% to 75% of reactions.
Lieberman In Allergy: Principles and Practice Mosby, 2003
Slide 16 04/18/23
Incidence of Anaphylaxis to Specific Agents 4
Non Steroidal Anti-Inflammatory Drugs (NSAIDs) Incidence varies depending on whether
asthmatic subjects are included
NSAIDs probably second most common
offending drug next to antibiotics.
Lieberman In Allergy: Principles and Practice Mosby, 2003
Slide 17 04/18/23
Incidence of Anaphylaxis to Specific Agents 5
Antisera Heterologous antisera to treat snake bites (4.6%
to 10%) Immunosuppression, incidence for anti-
lymphocyte globulin as high as 2%
Idiopathic Estimated to be between 20,592 and 47,024 cases
in USA – deaths rare
Lieberman in Allergy: Principles and Practice Mosby 2003
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Allergen Immunotherapy
• Incidence of systemic reaction from 0.8% to 46.7% depending on the dose of allergen and schedule used.
Deaths occur at a rate of 1 per 2,000,000 injections.
Stewart and Lockey JACI 1992
Kemp et al In: Allergens and Allergen Immunotherapy Marcel Dekker, 2004
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Signs and Symptoms of Anaphylaxis
Diffuse erythema Diffuse pruritus Diffuse urticaria Angioedema Bronchospasm Laryngeal edema Hyperperistalsis Hypotension
Cardiac arrhythmias Nausea Vomiting Lightheadedness Headache Feeling of impending doom Unconsciousness Flushing
Kemp and Lockey JACI 2002
Slide 20 04/18/23
Differential Diagnostic Considerations in Anaphylaxis
Vasovagal reactions Idiopathic flushing Mastocytosis Carcinoid syndrome Anxiety-induced hyperventilation Globus hystericus Serum sickness C-1 esterase inhibitor deficiency Shock-associated with myocardial infarction, blood loss, septicemia Scombroid poisoning
Montanaro and Bardana JACI 2002
Slide 21 04/18/23
Comments About Signs and Symptoms
of Anaphylaxis Urticaria or angioedema and flush most common ( > 90%). Cutaneous manifestations may be delayed or absent Next most common manifestations are respiratory (40% to 60%). Next are dizziness, unconsciousness (30% to 35%). Gastrointestinal symptoms (20% to 30%). More rapid onset, more likely serious. Signs and symptoms within 5 to 30 minutes, but may not develop for hours.
Lieberman In Allergy: Principles and Practice Mosby, 2003
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Agents that Cause Anaphylaxis 1Anaphylactic (IgE-Dependent) Foods (peanut, tree nuts,
and crustaceans) Milk, egg and fish also
important, especially in children
Medications (antibiotics) Venoms Latex Allergen vaccines Hormones Animal or human proteins Diagnostic allergens
Muscle relaxants Colorants (insect-derived, such as
carmine) Enzymes Polysaccharides Aspirin and other non-
steroidal anti-inflammatory drugs (probably)
Exercise (possibly, in food and medication-dependent events)
Kemp Immunol Allergy Clin N Am 2001
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Agents that Cause Anaphylaxis 2 (Allergic but not IgE Mediated)
Immune aggregates (Type II)
Intravenous immunoglobulin
Dextran (possibly)
Cytotoxic (Type III)
Transfusion reactions to cellular elements (IgG, IgM)
Kemp Immunol Allergy Clin N Am 2001
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Agents that Cause Anaphylaxis 3 (Non-allergic or IgE-independent)
Multimediator complement activation/activation of contact system: Radiocontrast media
Ethylene oxide gas on dialysis tubing
Protamine (possibly)
ACE-inhibitor administered during renal dialysis with sulfonated polyacrylonitrile, cuprophane, or polymethylmethacrylate dialysis membranes
Kemp Immunol Allergy Clin N Am 2001
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Agents that Cause Anaphylaxis 4(Non-allergic or IgE Independent)
Nonspecific degranulation of mast cellsand basophils
Opiates
Idiopathic
Physical factors:
Exercise Temperature (cold, heat)
Kemp Immunol Allergy Clin N Am 2001
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-Adrenergic Blockade By mouth or topically.
Paradoxical bradycardia, profound hypotension,and severe bronchospasm.
Can exacerbate disease and may impede treatment.
Selective β-blockers do not produce clinically significant adverse respiratory effects in mild-moderate asthma (including COPD). Not studied in anaphylaxis.
Toogood CMAJ 1987
Kivity and Yarchovsky JACI 1990
Salpeter, Ormiston, Salpeter Annals Int Med 2002
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Recurrent and Persistent Anaphylaxis
Recurrent or biphasic anaphylaxis occurs 8 to 12 hours in up to 20%.
Subjects with biphasic do not differ clinically but more epinephrine may be necessary for initial symptoms.
Persistent anaphylaxis may last from 5 to 32 hours.
Lee and Greenes Pediatrics, 2000
Kemp and deShazo In: Allergens and Allergen Immunotherapy to Treat Allergic Diseases. Marcel Dekker, 2004
Slide 28 04/18/23
Physician-Supervised Management of Anaphylaxis 1
I. Immediate Intervention a) Assessment of airway, breathing, circulation, and
mentation.
b) Administer EPI, 1:1000 dilution, 0.3 - 0.5 ml (0.01 mg/kg in children, max 0.3 mg dosage) IM, to
control SX and BP. Repeat, as necessary.
Kemp and Lockey JACI 2002
Simons et al JACI 1998
Simons, Gu, Simons JACI 2001
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Physician-Supervised Management of Anaphylaxis 2
I. Immediate Intervention continued c) IM into the anterolateral thigh (vastus lateralis)
produces higher & more rapid peak plasma level versus SQ & IM in arm. Therefore, with moderate, severe, or progressive ANA, EPI IM into anterolateral thigh. Alternatively, an EPI autoinjector given through clothing in same manner. Repeat, as necessary.
Kemp and Lockey JACI 2002
Simons et al JACI 1998
Simons, Gu, Simons JACI 2001
Slide 30 04/18/23
Physician-Supervised Management of Anaphylaxis 3
I. Immediate Intervention - continued
d) Aqueous EPI 1:1000, 0.1- 0.3ml in 10ml NS (1:100,000 to 1:33,000 dilution), IV over several minutes prn.
e) For potentially moribund subjects, tubercular syringe, EPI 1:1000, 0.1 ml, insert into vein (IV), aspirate 0.9 ml of blood (1:10,000 dilution). Give as necessary for response.
Kemp and Lockey JACI 2002
Slide 31 04/18/23
Physician-Supervised Management of Anaphylaxis 4
II. General measures
a) Place in recumbent position and elevate lower extremities.
b) Maintain airway (endotracheal tube or cricothyrotomy).
c) O2, 6 - 8 liters/minute.
d) NS, IV. If severe hypotension, give volume expanders (colloid solution). e) Venous tourniquet above reaction site. Question if decreases absorption of allergen.
Kemp and Lockey JACI 2002
Slide 32 04/18/23
Physician-Supervised Management of Anaphylaxis 4
III. Specific Measures that Depend on Clinical Scenario
a) Aqueous EPI 1:1,000, ½ dose (0.1- 0.2 mg) at reaction site.
b) Diphenhydramine, 50 mg or more in divided doses orally or IV, maximum daily dose 200 mg (5 mg/kg) for children and 400 mg for adults.
c) Ranitidine, 50 mg in adults and 12.5 - 50 mg (1 mg/kg) in children, dilute in 5% G/W, total 20 ml,
inject IV, over 5 minutes. (Cimetidine 4 mg/kg OK for adults, not established for pediatrics).
Kemp and Lockey JACI 2002
Slide 33 04/18/23
Physician-Supervised Management of Anaphylaxis 5
III. Specific Measures that Depend on Clinical Scenario
d) Bronchospasm, nebulized albuterol 2.5 - 5 mg in 3 ml NS or levalbuterol 0.63 - 1.25 mg
as needed.
e) Aminophylline, 5mg/kg over 30 min IV may be helpful. Adjust dose based on age, medications, disease, current use.
f) Refractory hypotension, give dopamine, 400 mg in 500 ml G/W IV 2 - 20 μg/kg/min more or less.
Kemp and Lockey JACI 2002
Slide 34 04/18/23
Physician-Supervised Management of Anaphylaxis 6
III. Specific Measures that Depend on Clinical Scenario
g) Glucagon, 1- 5 mg (20 - 30 μg/kg [max 1 mg] in children), administered IV over 5 minutes followed with IV infusion 5-15 μg/min.
h) Methylprednisolone, 1- 2 mg/kg per 24 hr; prevents prolonged reactions and relapses.
Kemp and Lockey JACI 2002
Slide 35 04/18/23
Vasodepressor (Vaso-Vagal) Definition
Non-allergic reaction characterized by slow pulse nausea, pallor, sweating, clammy skin, and/or hypotension.
Kemp and Lockey JACI 2002
Slide 36 04/18/23
Vasodepressor (Vaso-Vagal)
Management
a) Place patient in supine position with elevated lower extremities.
b) For severe vasodepressor reaction ONLY (i.e., bradycardia, nausea, pallor, sweating, cool clammy skin, hypotension), atropine 0.3 - 0.5 mg (0.02 mg/kg) SQ every 10 minutes (max 2 mg/adult and 1 mg/child).
c) If hypotension persists, give IV fluids.
Kemp and Lockey JACI 2002
Slide 37 04/18/23
Measures to Reduce the Incidence of Drug- Induced Anaphylaxis and Anaphylactic Deaths 1
General Measures Obtain thorough history for drug allergy. Avoid drugs with immunological or biochemical
cross-reactivity with any agents to which the patient is sensitive.
Administer drugs orally rather than parenterally when possible.
Check all drugs for proper labeling
Keep patients in clinic for 20 to 30 minutes after injections.
Lieberman In: Allergy: Principles and Practice Mosby, 2003
Slide 38 04/18/23
Measures to Reduce the Incidence of Anaphylaxis and Anaphylactic Deaths 2
Measures for Patients at Risk
Avoid causative factor/s.
Have patient wear and carry warning identification.
Teach self-injection of epinephrine and caution patient to keep epinephrine kit with them.
Discontinue -adrenergic blocking agents, ACE inhibitors (controversial), monoamine oxidase inhibitors, and tricyclic antidepressants, where possible.
Lieberman In: Allergy: Principles and Practice. Mosby, 2003
Slide 39 04/18/23
Measures to Reduce the Incidence of Anaphylaxis and Anaphylactic Deaths 3
Measures for Patients at Risk
Use preventive techniques when patient is required to undergo a procedure or take an agent which places them at risk. Such techniques include:
Pretreatment Provocative challenge
Desensitization
Lieberman In: Allergy: Principles and Practice. Mosby, 2003
Slide 40 04/18/23
Summary
Prognosis
Factor Poor Good
Dose of antigen (allergen) Large Small
Onset of symptoms Early Late
Initiation of treatment LateEarly
Route of exposure ParenteralOral*
β-adrenergic blocker use Yes No
Presence of underlying disease Yes No
* True for drugs, not foods
Slide 41 04/18/23
Allergic Emergencies
Section 2: Upper Airway Oedema
Slide 42 04/18/23
Upper Airway Oedema Lecture Objectives
To understand the causes of angioedema;
To review the spectrum and management of hereditary angioedema;
To review Angiotensin Converting Enzyme (ACE) inhibitor related angioedema.
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Outline of Lecture Clinical description
Classification
Examples of life-threatening oedema:
Hereditary angioedema Acquired oedema Angiotensin enzyme inhibitor-induced oedema
Clinical description Pathophysiology Management
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Angioedema First described by Quincke in
1882 Well-demarcated non-pitting
oedema Caused by same pathological
factors that cause urticaria Reaction occurs deeper in
dermis and subcutaneous tissues
Face, tongue, lips, eyelids most commonly affected
May cause life-threatening respiratory distress if larynx involved
Slide 45 04/18/23
Classification of Angioedema 1
Hereditary Type 1: C1 esterase inhibitor deficiency Type 2: functional abnormality of C1 esterase
inhibitor
Acquired Idiopathic IgE-mediated Non-IgE-mediated Systemic disease Physical causes Other
Slide 46 04/18/23
Classification of Angioedema 2
IgE-mediated Drugs Foods Stings Infections (eg viral, helminthic)
Non-IgE-mediated Cyclooxygenase inhibition (ASA and other
NSAIDS) Angiotensin converting enzyme inhibition
Slide 47 04/18/23
Classification of Angioedema 3
Systemic diseases
Systemic lupus erythematosis
Hypereosinophilia
Lymphoma: abnormal antibodies activate complement
system
Slide 48 04/18/23
Classification of Angioedema 4
Physical causes Cold Cholinergic Solar Vibratory
Other Some contact reactions Autoantibodies to C1-esterase inhibitor Unopposed complement activation
Slide 49 04/18/23
Incidence
Chronic idiopathic urticaria/angioedema occurs in 0.1% population
65% remit within 3 years85% remit within 5 years95% remit within 10 years
Angioedema occurs most commonly with urticaria (40% cases)
May occur in isolation (10% cases)
Slide 50 04/18/23
Hereditary Angioedema (HAE)
1888 - family described by William Osler
1963 - Donaldson and Evans described the biochemical defect responsible - absence of C1
inhibitor
Slide 51 04/18/23
Hereditary Angioedema (HAE)
Subtypes
Type 1*
Autosomal dominant Markedly suppressed C1 esterase
inhibitor protein levels
* Accounts for 85% cases
Slide 52 04/18/23
Hereditary Angioedema (HAE)
Subtypes
Type 2*
Autosomal dominant, with a point mutation leading to synthesis of a dysfunctional protein
Functional assay required for diagnosis as level may be normal
* Accounts for 15% cases
Slide 53 04/18/23
Hereditary Angioedema (HAE)
Epidemiology 1:10,000 - 1:150,000 with no racial or gender predilection
Clinical manifestations Usually manifests in 2nd decade May be seen in young children Oedema may develop in one or several organs Presentation depends upon site of swelling Attacks last 2- 5 days before spontaneous resolution
Nzeako Arch Intern Med, 2001
Slide 54 04/18/23
Clinical Manifestations 1
Angioedema may develop in subcutaneous tissues of extremities, genitalia, face, trunk.
Slide 55 04/18/23
Clinical Manifestations 2
Oedema of wall of intestine may present as an acute abdominal emergency.
Submucosal oedema of larynx or pharynx may cause asphyxiation – this may occur on first presentation.
Bork Mayo Clin Proc 2000
Slide 56 04/18/23
Clinical Manifestations 3
Laryngeal oedema
Commonest cause of mortality in HAE Time from onset of swelling to death 1- 14 hours
(mean 7 hours) May be presenting feature Death may occur in those with no previous
laryngeal oedema episodes Increased risk within certain families Early symptoms - lump in throat, tightness in throat Hoarseness, dysphagia, progressive dyspnoea
Bork Mayo Clin Proc 2000
Slide 57 04/18/23
Hereditary Angioedema (HAE)
Diagnosis
Clinical presentation For screening - quantitative and functional
assays of C1 inhibitor C4 and C2 levels reduced in acute attack C4 persistently low in most patients
Nzeako Arch Intern Med 2001
Slide 58 04/18/23
Hereditary Angioedema (HAE)Pathophysiology 1
C1 inhibitor
Single chain glycoprotein; molecular weight 104,000; serine protease family
Important regulatory protein of complement cascade
Inactivates C1 esterase complex Regulates coagulation, fibrinolytic, kinin,
complement systems
Nielson Immunopharmacology 1996
Slide 59 04/18/23
Hereditary Angioedema (HAE) Pathophysiology 2
Lack of C1 inhibitor leads to abnormal activation of complement pathway, reduced C2 and C4 levels
Hageman factor induces formation of kallikrein from prekallikrein
Bradykinin is released from high molecular weight kininogen
All these mediators increase capillary permeability and are responsible for attacks of angioedema
Kaplan JACI 2002
Slide 60 04/18/23
Genetics
Autosomal dominant; all patients heterozygous
25% no prior family history - spontaneous mutations
More than 100 different mutations reported
Varied clinical pattern may be explained by variable effect of mutations on C1 inhibitor synthesis
Agostini Medicine (Baltimore) 1992
Slide 61 04/18/23
Hereditary Angioedema (HAE)Management
Principles
Action plan for acute episodes
Strategy for long term prophylaxis
Short term prophylaxis for high risk procedures
Regular follow up for education and monitoring side effects of therapy
Slide 62 04/18/23
Management 1
Acute attacks
Treatment of choice is C1 inhibitor concentrate, 500 - 1,000U intravenous infusion Safe and effective - no long term side effects reported Excellent and prompt response in most patients Not available in USA, but in clinical trials
Bork Arch Intern Med 2001
Slide 63 04/18/23
Management 2
Acute attacks when C1 inhibitor concentrate notavailable
Intubation and respiratory support may be necessary when laryngeal oedema present
Fresh frozen plasma (FFP) has been used successfully for acute attacks. Exacerbation of symptoms by supplying more kallikrein substrate is a theoretical consideration but is rarely seen
Bork Arch Intern Med 2001
Slide 64 04/18/23
Management 3
Long term – adults
Attenuated androgens (stanozolol, danazol, oxandrin) can prevent attacks
Increase levels of C1 inhibitor, C4 and C2
Titrate to lowest effective dose to control attacks - for danazol may be able to reduce to 200 mg/d every second day
Regular monitoring necessary
Nzeako Arch Intern Med 2001
Slide 65 04/18/23
Management 4
Long term – children
Antifibrinolytic agents have been used as first line prophylaxis
Low dose danazol
Nzeako Arch Intern Med 2001
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Management 5
Short term prophylaxis
Necessary for high risk interventions, eg, dental procedures, tonsillectomy
C1 inhibitor concentrate, where available, given before procedure
Increasing dose of attenuated androgen for a few days beforehand
Fresh frozen plasma
Slide 67 04/18/23
Management 6
Other
Avoid oral contraceptive pill, ACE inhibitor medication Premedicate before procedures requiring
radiocontrast media or streptokinase as they may decrease C1 inhibitor levels
Reassurance; address issues such as ongoing stress Treat infections promptly Genetic counseling and screening
Slide 68 04/18/23
Acquired Angioedema (AAE) 1
Type 1 Associated with rheumatologic diseases, B cell
lymphoproliferative disorders
Activation of complement by complexes of anti-idiotypic antibodies and surface immunoglobulins consumes C1 inhibitor so levels decline
Type 2 Development of autoantibodies against C1 inhibitor
Autoantibodies bind at active site on molecule leading to inactivation
Markovic Ann Int Med 2000
Slide 69 04/18/23
Acquired Angioedema (AAE) 2 Decreased C1q levels distinguish AAE from HAE where
C1q is usually normal
Treatment of underlying condition may result in resolution
For acute attacks, C1 inhibitor concentrate, where available should be used
Attenuated androgen may be useful in Type 1
Immunosuppressive therapy for Type 2
Laurent Clin Rev Allergy Immunol 1999
Slide 70 04/18/23
Angiotensin Converting Enzyme (ACE) Inhibitors and Angioedema 1
Angioedema develops in 0.1% to 0.5% of those receiving the drug
Onset from 1st week of use to 2 - 3 years of use Symptoms resolve within 24 - 48 hours of cessation of
drug Most commonly seen with captopril and enalopril but
described with all in class Genetic factors may be important Subjects with a history of angioedema from other
causes are more susceptible to ACE-induced angioedema
Slater JAMA 1988
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Angiotensin Converting Enzyme (ACE) Inhibitors and Angioedema 2
Face and lips most commonly involvedbut laryngeal oedema reported
Risk factors include obesity, prior endotracheal intubation and face and neck surgery
ACE inhibitors will trigger attacks in those with HAE so avoid in these patients
Jain Chest 1992
Slide 72 04/18/23
Angiotensin Converting Enzyme (ACE) Inhibitors and Angioedema 3
Pathophysiology
ACE inhibitors may cause bradykinin accumulation resulting in vasodilatation, capillary leakage and angioedema
Patients may have a congenital or acquired impairment of kininase 1 which degrades bradykinin leading to bradykinin accumulation once ACE is blocked
Slide 73 04/18/23
Angiotensin Converting Enzyme (ACE) Inhibitors and Angioedema 4
Management
Stop drug and use other classes of antihypertensive agents
ALL ACE inhibitors are to be avoided Management of angioedema depends on site of
involvement - securing the airway by intubation may be necessary
ACE receptor antagonists are generally considered to be safe
Slide 74 04/18/23
Angioedema - Conclusions
Most often occurs in association with urticaria When angioedema occurs alone, consider HAE,
AAE HAE is a rare disease but must be identified as it
can be life-threatening Refer to appropriate specialist for ongoing
management ACE-inhibitor induced angioedema is an
important cause in older people
Slide 75 04/18/23
Allergic Emergencies
Section 3: Severe Asthma Exacerbations
Slide 76 04/18/23
Lecture Objectives
At the end of this lecture participants will be able to:
Understand the risk factors for asthma exacerbations;
Identify the signs and symptoms of acute asthma;
Outline appropriate treatment strategies.
Slide 77 04/18/23
Features of a Severe Asthma Exacerbation
One or more present:
Use of accessory muscles of respiration Pulsus paradoxicus >25 mm Hg Pulse > 110 BPM Inability to speak sentences Respiratory rate >25 - 30 breaths/min PEFR or FEV1 < 50% predicted SaO2 <91- 92%
McFadden Am J Respir Crit Care Med 2003
Slide 78 04/18/23
Risk Factors for Fatal or Near-Fatal Asthma Attacks
Previous episode of near-fatal asthma Multiple prior ER visits or hospitalizations Poor compliance with medical treatments Adolescents or inner city asthmatics (USA) African-Americans>Hispanics>Caucasians Allergy to Alternaria Recent use of oral CCS Inadequate therapy:
Excessive use of β-agonists No inhaled CCS Concomitant β-blockers
Ramirez and Lockey In: Asthma, American College of Physicians, 2002
Slide 79 04/18/23
Physical Findings in Severe Asthma Exacerbations
Tachypnea Tachycardia Wheeze Hyperinflation Accessory muscle use Pulsus paradoxicus Diaphoresis Cyanosis Sweating Obtundation
Brenner, Tyndall and Crain In: Emergency Asthma. Marcel Dekker 1999
Slide 80 04/18/23
Causes of Asthma Exacerbations
Lower or upper respiratory infections Cessation or reduction of medication Concomitant medication, e.g. β-blocker Allergen or pollutant exposure
Slide 81 04/18/23
Differential Diagnosis
COPD Bronchitis Bronchiectasis Endobronchial
diseases Foreign bodies Extra- or intra-thoracic
tracheal obstruction Cardiogenic
pulmonary edema
Non-cardiogenic pulmonary edema
Pneumonia Pulmonary emboli Chemical pneumonitis Hyperventilation
syndrome Pulmonary embolus Carcinoid syndrome
Brenner, Tyndall, Crain In: Emergency Asthma. Marcel Dekker, 1999
Slide 82 04/18/23
Peak Flow Meters Use peak flow meters to monitor asthma and prevent exacerbations: Inexpensive Easy to use Accurate Provide “real life” measurements at worst and best times of the day Provide objective measurement of pulmonary function Detect early changes of asthma worsening
Slide 83 04/18/23
Patient “Self Management”
If personal best peak flow measurements: Fall 10+%, double dose of inhaled CCS Fall 20+%, use short-acting bronchodilator Q4
-6 hour, plus 2 x inhaled CCS Call office, try to determine if infection is
present Fall 40 - 50%, add oral CCS Fall greater than 50%, urgent visit to either
Outpatient office Emergency room
Kaliner In: Current Review of Asthma. Curent Medicine, 2003
Slide 84 04/18/23
Stages of Asthma Exacerbations Stage 1:
Symptoms Somewhat short of breath Can lie down and sleep through the night Cannot perform full physical activities without shortness of
breath
Signs Some wheezes on examination Respiratory rate, 15 (normal <12) Pulse 100 Peak flows and spirometry reduced by 10%
Slide 85 04/18/23
Stages of Asthma Exacerbations Stage 2:
Symptoms Less able to do physical activity due to shortness of
breath Dyspnea on walking stairs May wake up at night short of breath Uncomfortable on lying down Some use of accessory muscles of respiration
Signs Wheezing Respiratory rate 18 Pulse 111 Peak flows and spirometry reduced by 20+%
Slide 86 04/18/23
Stages of Asthma Exacerbations Stage 3:
Symptoms Unable to perform physical activity without
shortness of breath Cannot lie down without dyspnea Speaks in short sentences Using accessory musclesSigns Wheezing Respiratory rate 19 - 20 Pulse 120 Peak flows and spirometry reduced by 30+%
Slide 87 04/18/23
Stages of Asthma Exacerbations Stage 4:
Symptoms Sitting bent forward Unable to ambulate without shortness of breath Single word sentences Mentally-oriented and alert Use of accessory muscles
Signs Wheezing less pronounced than anticipated Respiratory rate 20 - 25 Pulse 125+ Peak flows and spirometry reduced by 40+% SaO2 91- 92%
Slide 88 04/18/23
Stages of Asthma Exacerbations Stage 5:
Symptoms Reduced consciousness Dyspnea Silent chest – no wheezing
Signs Fast, superficial respiration Respiratory rate >25 Unable to perform peak flows or spirometry Pulse 130 - 150+ SAO2 <90
Slide 89 04/18/23
Severity of Asthma as Graded by % Predicted FEV1
FEV% predicted Severity 70 - 100 Mild 60 - 69 Moderate 50 - 59 Moderately severe 35 - 49 Severe < 35 Very severe
(life-threatening)
Slide 90 04/18/23
Treatment of Asthma Exacerbations 1
Preferred treatment choices β2-agonists
Inhaled by MDI or nebulizer Injected
Anticholinergics Inhaled by MDI or nebulizer
Corticosteroids Parenteral, oral or inhaled
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Treatment of Asthma Exacerbations 2
Secondary treatment choices Aminophylline or theophylline (oral,
parenteral) Leukotriene receptor antagonists (oral) Oxygen Magnesium sulfate
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Treatment of Asthma Exacerbations 3Beta Agonists
Inhaled is preferred route
MDI plus spacer, 4 - 8 puffs Q 20 min x 3 Nebulizer, 2.5 - 5 mg albuterol Q 20 min x 3 Epinephrine SQ, 0.3 - 0.5ml (0.01 ml/kg children) Levalbuterol, 0.63 - 1.25 mg Q 4 - 8 hours (if
available)
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Treatment of Asthma Exacerbations 4Anticholinergics
Ipratropium
Preferred use: combined with beta agonist MDI plus spacer, 2 - 4 puffs Q 20 min x 3 Nebulizer, 500 μg Q 20 min x 3
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Treatment of Asthma Exacerbations 5Corticosteroids
No immediate effect Earliest effects 6 hours after high dose Oral is as effective as parenteral Prednisone (equivalent), 45 - 60 mg Higher doses have increased side effects and no
appreciable increased therapeutic benefit Methylprednisolone, 1 – 2 mg/kg/24 hours No substantial data for usefulness in acute
setting
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Treatment of Asthma Exacerbations 6 Aminophylline and Theophylline
Controversial: Added no benefit to inhaled beta agonists Increased complications
Loading dose for aminophylline: 5 – 6 mg/kg over 20 - 30 min
Maintenance dose: 0.4 mg/kg/hr (adjust for heart and liver disease)
Try to achieve 5 - 15 μg/ml, monitor plasma levels to adjust dose
Doses for theophylline similar but slightly less
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Treatment of Asthma Exacerbations 7 Leukotriene Modifiers
Few studies Suggest usefulness in reducing hospitalizations Montelukast, 10 mg orally Zafirlukast, 20 mg orally
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Treatment of Asthma Exacerbations 8 Magnesium Sulfate
Controversial: Inconsistent data
Used in very severe asthma in emergency settings:
FEV1 < 25% predicted Other signs of severe disease
1.2 - 2 gm IV over 10 - 20 min in 50 ml saline Minor side effects
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Preventing Exacerbations 1Oral Corticosteroids
Oral corticosteroids are the most powerful medications available to reduce airway inflammation
Use until attack completely abated: PEFR and FEV1 at baseline levels Symptoms gone
Taper to QOD and determine if patient can remain well if corticosteroids are withdrawn completely
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Preventing Exacerbations 2 Inhaled Corticosteroids
Place patient on high dose inhaled corticosteroids Fluticasone, 880 - 1760 μg Budesonide, 800 - 1600 μg
Once oral corticosteroids are withdrawn, reduce the inhaled dose incrementally, while maintaining PEFR at personal best level
Consider combination of long acting β2-agonist and inhaled corticosteroid in order to achieve the lowest dose of corticosteroid possible
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Preventing Exacerbations 3Underlying Causes and Patient Education
Evaluate patient for: Allergy Infection Compliance Inappropriate concomitant medications Social factors Tobacco, drugs, irritants, fumes Psychiatric disorders
Patient education www.anafylaxis.nl
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World Allergy Organization (WAO)
For more information on the World Allergy Organization (WAO), please visit www.worldallery.org or contact the:
WAO Secretariat555 East Wells Street, Suite 1100
Milwaukee, WI 53202United States
Tel: +1 414 276 1791Fax: +1 414 276 3349
Email: info@worldallergy.org
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