Transcript GLORIA Module 3 Allergic Emergencies

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GLORIA Module 3
Allergic Emergencies
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Allergic Emergencies
WAO Expert Panel
Authors:
Richard F Lockey, USA
Connie H Katelaris, Australia
Michael Kaliner, USA
Contributors:
F.Estelle R. Simons, Canada
Daniel Vervloet, France
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Allergic Emergencies
Section 1: Anaphylaxis
Section 2: Upper Airway Oedema
Section 3:
Severe Asthma Exacerbations
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Allergic Emergencies
Section 1: Anaphylaxis
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Anaphylaxis Lecture Objectives
After this lecture, participants will:
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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.
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Definition of Anaphylaxis
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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
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Gell and Coombs’ Hypersensitivity
(immunopathologic reactions)
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Type I
Type II
Type III
Type IV
Immediate
Cytotoxic
Immune Complex
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
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Degranulation of mast cells and basophils.
Preformed granule-associated substances, e.g.,
histamine, tryptase, chymase, heparin, histaminereleasing 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
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Shock Organs in Anaphylaxis
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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
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Incidence
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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
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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
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Incidence of Anaphylaxis to Specific Agents 1
Antibiotics
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Most common cause of drug induced anaphylaxis.
Latex
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Increased incidence last decade.
Population at risk includes multiple mucosal
exposure to latex (catheterization & surgery) and
healthcare workers.
Radiocontrast agents
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Introduction of lower osmolarity agents
reduced reaction rate
Lieberman In: Allergy: Principles and Practice. Mosby, 2003
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Incidence of Anaphylaxis to Specific Agents 2
Hymenoptera stings
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Incidence ranges from 0.4% to 5%
Estimated fatalities 100 per year in U.S.A.
Food
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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
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Incidence of Anaphylaxis to Specific Agents 3
Perioperative anaphylaxis
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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
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Incidence of Anaphylaxis to Specific Agents 4
Non Steroidal Anti-Inflammatory Drugs
(NSAIDs)
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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
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Incidence of Anaphylaxis to Specific
Agents 5
Antisera
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Heterologous antisera to treat snake bites (4.6%
to 10%)
Immunosuppression, incidence for antilymphocyte globulin as high as 2%
Idiopathic
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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
•
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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
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Diffuse erythema
Diffuse pruritus
Diffuse urticaria
Angioedema
Bronchospasm
Laryngeal edema
Hyperperistalsis
Hypotension
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Cardiac arrhythmias
Nausea
Vomiting
Lightheadedness
Headache
Feeling of impending doom
Unconsciousness
Flushing
Kemp and Lockey JACI 2002
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Differential Diagnostic
Considerations in Anaphylaxis
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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
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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.
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Lieberman In Allergy: Principles and Practice Mosby, 2003
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Agents that Cause Anaphylaxis 1
Anaphylactic (IgE-Dependent)
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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
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Muscle relaxants
Colorants
(insect-derived, such as
carmine)
Enzymes
Polysaccharides
Aspirin and other nonsteroidal antiinflammatory drugs
(probably)
Exercise (possibly, in
food and medicationdependent 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)
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Intravenous immunoglobulin
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Dextran (possibly)
Cytotoxic (Type III)
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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:
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Radiocontrast media
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Ethylene oxide gas on dialysis tubing
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Protamine (possibly)
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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 cells
and basophils
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Opiates
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Idiopathic
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Physical factors:
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Exercise
Temperature (cold, heat)
Kemp Immunol Allergy Clin N Am 2001
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-Adrenergic Blockade
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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 mildmoderate 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%.
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Subjects with biphasic do not differ clinically but
more epinephrine may be necessary for initial
symptoms.
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Persistent anaphylaxis may last from 5 to 32 hours.
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Lee and Greenes Pediatrics, 2000
Kemp and deShazo In: Allergens and Allergen
Immunotherapy to Treat Allergic Diseases. Marcel Dekker, 2004
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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
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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
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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
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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
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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
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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
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Vasodepressor (Vaso-Vagal)
Definition
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Non-allergic reaction characterized by slow pulse
nausea, pallor, sweating, clammy skin, and/or
hypotension.
Kemp and Lockey JACI 2002
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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
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Measures to Reduce the Incidence of DrugInduced Anaphylaxis and Anaphylactic
Deaths 1
General Measures
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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
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Measures to Reduce the Incidence of
Anaphylaxis and Anaphylactic Deaths 2
Measures for Patients at Risk
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Avoid causative factor/s.
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Have patient wear and carry warning identification.
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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
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Measures to Reduce the Incidence of
Anaphylaxis and Anaphylactic Deaths 3
Measures for Patients at Risk
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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
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Summary
Prognosis
Factor
Poor
Good
Dose of antigen (allergen)
Large
Small
Onset of symptoms
Early
Late
Initiation of treatment
Late
Early
Route of exposure
Parenteral
Oral*
β-adrenergic blocker use
Yes
No
Presence of underlying disease
Yes
No
* True for drugs, not foods
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Allergic Emergencies
Section 2: Upper Airway Oedema
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Upper Airway Oedema
Lecture Objectives
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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
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Clinical description
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Classification
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Examples of life-threatening oedema:
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Hereditary angioedema
Acquired oedema
Angiotensin enzyme inhibitor-induced oedema
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Clinical description
Pathophysiology
Management
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Angioedema
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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
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Classification of Angioedema 1
Hereditary
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Type 1: C1 esterase inhibitor deficiency
Type 2: functional abnormality of C1 esterase
inhibitor
Acquired
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Idiopathic
IgE-mediated
Non-IgE-mediated
Systemic disease
Physical causes
Other
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Classification of Angioedema 2
IgE-mediated
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Drugs
Foods
Stings
Infections (eg viral, helminthic)
Non-IgE-mediated
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Cyclooxygenase inhibition (ASA and other
NSAIDS)
Angiotensin converting enzyme inhibition
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Classification of Angioedema 3
Systemic diseases
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Systemic lupus erythematosis
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Hypereosinophilia
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Lymphoma:
abnormal antibodies activate complement
system
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Classification of Angioedema 4
Physical causes
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Cold
Cholinergic
Solar
Vibratory
Other
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Some contact reactions
Autoantibodies to C1-esterase inhibitor
Unopposed complement activation
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Incidence
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Chronic idiopathic urticaria/angioedema occurs
in 0.1% population
65% remit within 3 years
85% remit within 5 years
95% remit within 10 years
Angioedema occurs most commonly with
urticaria (40% cases)
May occur in isolation (10% cases)
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Hereditary Angioedema (HAE)
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1888 - family described by William Osler
1963 - Donaldson and Evans described the
biochemical defect responsible - absence of C1
inhibitor
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Hereditary Angioedema (HAE)
Subtypes
Type 1*
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Autosomal dominant
Markedly suppressed C1 esterase
inhibitor protein levels
* Accounts for 85% cases
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Hereditary Angioedema (HAE)
Subtypes
Type 2*
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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
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Hereditary Angioedema (HAE)
Epidemiology
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1:10,000 - 1:150,000 with no racial or gender
predilection
Clinical manifestations
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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
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Clinical Manifestations 1
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Slide 54
Angioedema may
develop in
subcutaneous tissues
of extremities,
genitalia, face, trunk.
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Clinical Manifestations 2
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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
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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
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Bork Mayo Clin Proc 2000
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Hereditary Angioedema (HAE)
Diagnosis
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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
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Hereditary Angioedema (HAE)
Pathophysiology 1
C1 inhibitor
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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
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Hereditary Angioedema (HAE)
Pathophysiology 2
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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
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Genetics
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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
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Hereditary Angioedema (HAE)
Management
Principles
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Action plan for acute episodes
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Strategy for long term prophylaxis
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Short term prophylaxis for high risk procedures
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Slide 61
Regular follow up for education and monitoring
side effects of therapy
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Management 1
Acute attacks
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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
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Management 2
Acute attacks when C1 inhibitor concentrate not
available
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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
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Management 3
Long term – adults
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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
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Management 4
Long term – children
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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
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Slide 66
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
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Management 6
Other
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Slide 67
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
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Acquired Angioedema (AAE) 1
Type 1
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
Associated with rheumatologic diseases, B cell
lymphoproliferative disorders
Activation of complement by complexes of antiidiotypic 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
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7/17/2015
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
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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 involved
but 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
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Angiotensin Converting Enzyme (ACE)
Inhibitors and Angioedema 3
Pathophysiology


Slide 72
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
7/17/2015
Angiotensin Converting Enzyme (ACE)
Inhibitors and Angioedema 4
Management




Slide 73
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
7/17/2015
Angioedema - Conclusions





Slide 74
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
7/17/2015
Allergic Emergencies
Section 3:
Severe Asthma Exacerbations
Slide 75
7/17/2015
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.
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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
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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
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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 79
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Causes of Asthma Exacerbations




Slide 80
Lower or upper respiratory infections
Cessation or reduction of medication
Concomitant medication, e.g. β-blocker
Allergen or pollutant exposure
7/17/2015
Differential Diagnosis







COPD
Bronchitis
Bronchiectasis
Endobronchial
diseases
Foreign bodies
Extra- or intrathoracic 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 81
7/17/2015
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 82
7/17/2015
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 83
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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




Slide 84
Some wheezes on examination
Respiratory rate, 15 (normal <12)
Pulse 100
Peak flows and spirometry reduced by 10%
7/17/2015
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




Slide 85
Wheezing
Respiratory rate 18
Pulse 111
Peak flows and spirometry reduced by 20+%
7/17/2015
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 muscles
Signs




Slide 86
Wheezing
Respiratory rate 19 - 20
Pulse 120
Peak flows and spirometry reduced by 30+%
7/17/2015
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





Slide 87
Wheezing less pronounced than anticipated
Respiratory rate 20 - 25
Pulse 125+
Peak flows and spirometry reduced by 40+%
SaO2 91- 92%
7/17/2015
Stages of Asthma Exacerbations
Stage 5:
Symptoms



Reduced consciousness
Dyspnea
Silent chest – no wheezing
Signs





Slide 88
Fast, superficial respiration
Respiratory rate >25
Unable to perform peak flows or spirometry
Pulse 130 - 150+
SAO2 <90
7/17/2015
Severity of Asthma as Graded by %
Predicted FEV1
FEV% predicted





Slide 89
70 - 100
60 - 69
50 - 59
35 - 49
< 35
7/17/2015
Severity
Mild
Moderate
Moderately severe
Severe
Very severe
(life-threatening)
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






Slide 90
7/17/2015
Treatment of Asthma Exacerbations 2
Secondary treatment choices




Slide 91
Aminophylline or theophylline (oral,
parenteral)
Leukotriene receptor antagonists (oral)
Oxygen
Magnesium sulfate
7/17/2015
Treatment of Asthma Exacerbations 3
Beta Agonists
Inhaled is preferred route




Slide 92
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)
7/17/2015
Treatment of Asthma Exacerbations 4
Anticholinergics
Ipratropium



Slide 93
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 5
Corticosteroids







Slide 94
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
7/17/2015
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






Slide 95
7/17/2015
Treatment of Asthma Exacerbations 7
Leukotriene Modifiers




Slide 96
Few studies
Suggest usefulness in reducing hospitalizations
Montelukast, 10 mg orally
Zafirlukast, 20 mg orally
7/17/2015
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






Slide 97
7/17/2015
Preventing Exacerbations 1
Oral 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



Slide 98
Taper to QOD and determine if patient can remain
well if corticosteroids are withdrawn completely
7/17/2015
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
Slide 99
7/17/2015
Preventing Exacerbations 3
Underlying 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
Slide 100
7/17/2015
World Allergy Organization (WAO)
For more information on the World Allergy Organization
(WAO), please visit www.worldallery.org or contact the:
WAO Secretariat
555 East Wells Street, Suite 1100
Milwaukee, WI 53202
United States
Tel: +1 414 276 1791
Fax: +1 414 276 3349
Email: [email protected]
Slide 101
7/17/2015