GLORIA Module 3:
Allergic Emergencies
Updated: June 2011
Global Resources in Allergy
(GLORIA™)
Global Resources In Allergy (GLORIA™) is the
flagship program of the World Allergy
Organization (WAO). Its curriculum educates
medical professionals worldwide through
regional and national presentations. GLORIA
modules are created from established guidelines
and recommendations to address different
aspects of allergy-related patient care.
World Allergy Organization (WAO)
The World Allergy Organization
is an international coalition of 89
regional and national allergy and
clinical immunology societies.
WAO’s Mission
WAO’s mission is to be a global resource
and advocate in the field of allergy,
advancing excellence in clinical care,
education, research and training through a
world-wide alliance of allergy and clinical
immunology societies
GLORIA Module 3:
Allergic Emergencies
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
Allergic Emergencies
Section 1: Anaphylaxis
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.
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
Gell and Coombs’ Hypersensitivity
(immunopathologic reactions)
•
•
•
•
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
Biochemical mediators
and chemotactic substances
• 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 antiinflammatory role (e.g., metabolism of vasoactive
mediators).
Kemp and Lockey JACI 2002
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
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.
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.
Neugut, Ghatak, Miller Arch Int Med 2001
Simons, Peterson, Black JACI 2002
Rangaraj, Tuthill, Burr, Alfaham JACI 2002
Incidence of anaphylaxis to
specific agents 1
Antibiotics
• 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
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
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
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
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
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
Signs and symptoms of anaphylaxis
•
•
•
•
•
•
•
•
Diffuse erythema
Diffuse pruritus
Diffuse urticaria
Angioedema
Bronchospasm
Laryngeal edema
Hyperperistalsis
Hypotension
Kemp and Lockey JACI 2002
•
•
•
•
•
•
•
•
Cardiac arrhythmias
Nausea
Vomiting
Lightheadedness
Headache
Feeling of impending doom
Unconsciousness
Flushing
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
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
Agents that cause anaphylaxis 1
anaphylactic (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
Kemp Immunol Allergy Clin N Am 2001
• Muscle relaxants
• Colorants
(insect-derived, such as carmine)
• Enzymes
• Polysaccharides
• Aspirin and other non-steroidal antiinflammatory drugs (probably)
• Exercise (possibly, in food and
medication-dependent events)
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
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
Agents that cause anaphylaxis 4
(non-allergic or IgE independent)
Nonspecific degranulation of mast cells and basophils
 Opiates
 Idiopathic
 Physical factors:
 Exercise
 Temperature (cold, heat)
Kemp Immunol Allergy Clin N Am 2001
-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
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
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
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
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
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
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
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
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
Vasodepressor (Vaso-Vagal)
Definition
•
Non-allergic reaction characterized by slow pulse
nausea, pallor, sweating, clammy skin, and/or
hypotension
Kemp and Lockey JACI 2002
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
Measures to reduce the incidence of druginduced 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
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
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
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
Allergic Emergencies
Section 2: Upper Airway
Oedema
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.
Outline of lecture
• Clinical description
• Classification
• Examples of life-threatening oedema:
– Hereditary angioedema
– Acquired oedema
– Angiotensin enzyme inhibitor-induced oedema
• Clinical description
• Pathophysiology
• Management
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
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
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
Classification of angioedema 3
Systemic diseases
• Systemic lupus erythematosis
• Hypereosinophilia
• Lymphoma:
abnormal antibodies activate complement system
Classification of angioedema 4
Physical causes
• Cold
• Cholinergic
• Solar
• Vibratory
Other
• Some contact reactions
• Autoantibodies to C1-esterase inhibitor
• Unopposed complement activation
Incidence
• 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)
Hereditary Angioedema (HAE)
• 1888 - family described by William Osler
• 1963 - Donaldson and Evans described the biochemical
defect responsible - absence of C1 inhibitor
Hereditary Angioedema (HAE)
Subtypes
Type 1*
•
Autosomal dominant
•
Markedly suppressed C1 esterase
inhibitor protein levels
* Accounts for 85% cases
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
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
Clinical manifestations 1
• Angioedema may develop
in subcutaneous tissues of
extremities, genitalia, face,
trunk
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
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
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
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
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
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
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
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
Management 2
Acute attacks when C1 inhibitor concentrate not
available
• 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
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
Management 4
Long term – children
• Antifibrinolytic agents have been used as first line
prophylaxis
• Low dose danazol
Nzeako Arch Intern Med 2001
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
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
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
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
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
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
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
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
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
Allergic Emergencies
Section 3:
Severe Asthma Exacerbations
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
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
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
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
Causes of asthma exacerbations
•
•
•
•
Lower or upper respiratory infections
Cessation or reduction of medication
Concomitant medication, e.g. β-blocker
Allergen or pollutant exposure
Differential diagnosis
•
•
•
•
•
•
COPD
Bronchitis
Bronchiectasis
Endobronchial diseases
Foreign bodies
Extra- or intra-thoracic
tracheal obstruction
• Cardiogenic pulmonary
edema
Brenner, Tyndall, Crain In: Emergency Asthma. Marcel Dekker, 1999
• Non-cardiogenic
pulmonary edema
• Pneumonia
• Pulmonary emboli
• Chemical pneumonitis
• Hyperventilation
syndrome
• Pulmonary embolus
• Carcinoid syndrome
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
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
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%
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+%
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
• Wheezing
• Respiratory rate 19 - 20
• Pulse 120
• Peak flows and spirometry reduced by 30+%
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%
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
Severity of asthma as graded by %
predicted FEV1
FEV% predicted
Severity
•
•
•
•
•
Mild
Moderate
Moderately severe
Severe
Very severe
(life-threatening)
70 - 100
60 - 69
50 - 59
35 - 49
< 35
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
Treatment of asthma exacerbations 2
Secondary treatment choices
–
–
–
–
Aminophylline or theophylline (oral, parenteral)
Leukotriene receptor antagonists (oral)
Oxygen
Magnesium sulfate
Treatment of asthma exacerbations 3
beta 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)
Treatment of asthma exacerbations 4
anticholinergics
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
Treatment of asthma exacerbations 5
corticosteroids
•
•
•
•
•
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
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
Treatment of asthma exacerbations 7
leukotriene modifiers
•
•
•
•
Few studies
Suggest usefulness in reducing hospitalizations
Montelukast, 10 mg orally
Zafirlukast, 20 mg orally
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
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
• Taper to QOD and determine if patient can remain
well if corticosteroids are withdrawn completely
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
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
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: info@worldallergy.org