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Allergic

WAO Expert Panel


emergencies
Authors:
Richard F Lockey, USA
Connie H Katelaris, Australia
Michael Kaliner, USA
Contributors:
F.Estelle R. Simons, Canada
Daniel Vervloet, France

Allergy and Allergic


Emergencies

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
Type
I Immediate
Type II Cytotoxic
reactions)

Type III
Immune Complex
Type IVDelayed 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,
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

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 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 antilymphocyte globulin as high as 2%

Idiopathic
Estimated to be between 20,592 and
47,024 cases in USA deaths rare

Lieberman in
2003

Allergy:

Principles and Practice Mosby

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 nonsteroidal anti-inflammatory
drugs (probably)
Exercise (possibly, in food
and medication-dependent
events)

Agents that cause


anaphylaxis 2 (allergic
but not IgE mediated)
Immune aggregates (Type III)
Intravenous immunoglobulin
Dextran (possibly)

Cytotoxic (Type II)


Transfusion reactions to cellular
elements (IgG, IgM)
Kemp Immunol Allergy Clin N Am 2001

Agents that cause


anaphylaxis 3
(non-allergic or IgEMultimediator
complement activation/activation
independent)
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
Nonspecific degranulation of mast cells and
basophils
independent)
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 -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

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, 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 g/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 g/kg [max 1
mg] in
children), administered IV over 5
minutes followed
with IV infusion 5-15
g/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 drug- induced
anaphylaxis and anaphylactic
deaths 1
General Measures
Obtain thorough history for drug allergy
Avoid drugs with immunological or biochemical crossreactivity 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


Onset of symptoms

EarlyLate

Initiation of treatment
Route of exposure

Small

Late Early

Parenteral Oral*

-adrenergic blocker use

Yes

No

Presence of underlying disease Yes


* True for drugs, not foods

No

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 C 1 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 antiidiotypic antibodies and surface immunoglobulins
consumes C1 inhibitor so levels decline
Type 2
Development of autoantibodies against C 1 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
Previous asthma
episode of near-fatal
asthma
attacks

Multiple prior ER visits or hospitalizations


Poor compliance with medical treatments
Adolescents or inner city asthmatics
(USA) AfricanAmericans>Hispanics>Caucasians
Allergy to Alternaria
Recent use of oral CCS
Inadequate therapy:
Excessive use of -agonists
No inhaled CCS
Concomitant -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. -blocker
Allergen or pollutant exposure

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

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
Symptoms
stage 1:
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
Symptoms
stage 4:

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% predictedSeverity

70 - 100
60 - 69
50 - 59
35 - 49
< 35

Mild
Moderate
Moderately severe
Severe
Very severe
(life-threatening)

Treatment of asthma
exacerbations 1
Preferred treatment choices
2-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
x3
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 g Q 20 min x 3

Treatment of asthma
exacerbations 5
No immediate
effect
corticosteroids

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
Controversial:
Added no benefit to inhaled beta agonists
theophylline

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 g/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 g
Budesonide, 800 - 1600 g
Once oral corticosteroids are withdrawn, reduce the
inhaled dose incrementally, while maintaining PEFR
at personal best level
Consider combination of long acting 2-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

Drugs and the Biliary system


Formation of gallstones with cholesterol
content is the commonest pathological
condition of the biliary tract
Surgery is generally the preferred option
but there are drugs that dissolve noncalcified cholesterol gallstones
Ursodeoxycholic acid is the principal agent
used for this purpose

The pain produced by passage of gallstone


through the bile duct (biliary colic) can be
very intense requiring immediate relief
The following drugs may be used
Morphine relieves the pain effectively but
constricts the sphincter of Oddi and may
raise the pressure in the bile duct
Buprenorphine may be the preferable
option

Pethedine relieves the pain effectively


but relaxes other smooth muscle e.g. that
of the ureter
Atropine has antispasmodic action and is
commonly employed to relieve biliary
spasm, may be used in conjunction with
morphine
Nitrates can produce a marked fall of
intrabiliary pressure and may be used to
releve biliary spsams