SECTION V THORACIC AND RESPIRATORY DISORDERS
Asthma
Rita K. Cydulka and Craig G. Bates
KEY POINTS
Asthma is a chronic inflammatory condition that can be
controlled.
Indications of inadequate control of asthma include
frequent use of short-acting -agonist agents,
wheezing, coughing, and nighttime symptoms.
Emergency department treatment of asthma
exacerbation includes a targeted history and physical
examination, aerosolized -agonist agents, and
systemic steroids with objective measures of response
to therapy. Anticholinergic agents should be used in the
emergency department for patients with a severe
exacerbation.
At discharge, controller medications should be
prescribed in addition to rescue medications for
patients with chronic persistent asthma. Patients should
follow up with a primary care physician or asthma
specialist within several weeks.
PERSPECTIVE
Asthma is a chronic inflammatory disorder characterized by
increased responsiveness of the airways to multiple stimuli.
Many cells and cellular elements, such as mast cells, eosino-
phils, T lymphocytes, macrophages, neutrophils, and epithe-
lial cells, play a role in development of the inflammatory
response.1 The inflammation causes recurrent episodes of
wheezing, breathlessness, chest tightness, and coughing, par-
ticularly at night or in the early morning. These episodes are
associated with airflow obstruction that is reversible either
spontaneously or with treatment. Although patients appear to
clinically recover completely, evidence suggests that some
asthmatic patients have chronic airflow limitation. The recog-
nition that asthma is a chronic inflammatory disorder of the
airways has significant implications for the diagnosis, man-
agement, and potential prevention of acute exacerbations.
EPIDEMIOLOGY
Asthma affects approximately 4% to 5% of the population in
the United States.2 Although it is the most common chronic
disease of childhood, with a prevalence of 5% to 10%, it also
48
affects 7% to 10% of the elderly. Epidemiologic studies
suggest that asthma is underdiagnosed and undertreated in
all age groups. Part of the problem is that the transient
nature of asthma allows many patients to tolerate intermittent
respiratory symptoms before seeking medical care. Another
important factor resulting in underdiagnosis of asthma is the
sometimes nonspecific nature of the symptoms.
About half of cases of asthma develop before 10 years of
age and another third before 40 years. The 2:1 male-to-female
preponderance of asthma in childhood equalizes by 30 years
of age.3 The average asthmatic patient has 15 days of restricted
activity each year and spends 5.8 days in bed. Approximately
2 million emergency department (ED) visits, 484,000 hospi-
talizations, and more than 4000 deaths per year are attributed
to asthma. In the United States alone, the estimated direct
and indirect cost of asthma in all age groups was $56 billion
in 2007.4
PATHOPHYSIOLOGY
All asthmatic patients have hyperresponsive airways that
narrow when exposed to various stimuli: allergic, infectious,
pharmacologic, environmental, occupational, exercise related,
and emotional.
Allergic asthma occurs when inhaled allergens bind to
immunoglobulin E molecules bound to mast cells in the lining
of the tracheobronchial tree. During the early response,
various mediators are released and cause greater vascular
permeability, mucosal edema, and contraction of bronchial
smooth muscle. A second wave of reaction, the late response,
is seen hours to days later; it involves accumulation of inflam-
matory cells in the bronchial mucosa, thus perpetuating the
reaction. The release of mediators and regulation of the
inflammatory process in asthma are complex, redundant, and
self-perpetuating.5
Although several theories attempt to explain the patho-
physiologic changes that occur in nonallergic asthma, none
adequately explain all clinically observed phenomena.
Research suggests that even patients without atopy have
pathophysiology similar to that in atopic patients.5 Respira-
tory infections, particularly viral infections, may precipitate
bronchospasm. Viruses cause mucosal inflammation and
lower the firing threshold of the subendothelial vagal recep-
tors, which results in enhanced airway reactivity that may last
up to 8 weeks, even in nonasthmatic persons. Pharmacologic
agents, such as aspirin and nonsteroidal antiinflammatory
397
SECTION V Thoracic and Respiratory Disorders
compounds, coloring agents, and beta-blockers, also induce
acute asthma. In addition, sulfating agents, which are used
widely as food preservatives and antioxidants in pharmaceuti-
cal products, can exacerbate asthma.
A large variety of occupational dust and fumes may provoke
acute airway obstruction. Patients with occupational asthma
classically report a cyclic history; they are symptom free
during weekends, vacations, and on arrival at work. Exercise
may also stimulate an asthma attack. Exercise-induced bron-
chospasm is usually noted within 5 to 20 minutes after the
completion of exercise and is related to thermal changes in
the respiratory tree. Exercising in a cold, dry environment
causes a more marked response than does exercising in a
warm, humid environment. Finally, endocrine factors, such as
variations in progesterone and estradiol levels, also influence
asthma exacerbations, probably through modification of vagal
efferent activity.
Most patients with asthma seem to display an exaggerated
bronchoconstrictive response to a variety of exogenous and
endogenous stimuli, and inflammation plays a key role. The
final common pathway is as follows1:
Airway narrowing
Bronchial wall edema
Bronchial smooth muscle contraction
Mucosal plugging
Enhanced airway reactivity and remodeling of the airway
wall, which results in increased airway resistance
Decreased forced expiratory volumes and flow rates
Lung hyperinflation
Increased work of breathing
Ventilation-perfusion mismatch
PRESENTING SIGNS AND SYMPTOMS
When evaluated in the ED, many patients relay a history of
asthma, but some do not. Patients with a severe asthma attack
may be in obvious respiratory distress, with rapid breathing
and loud wheezing, but patients with mild exacerbation may
exhibit coughing and end-expiratory wheezing. The classic
symptoms of asthma consist of the triad of dyspnea, wheez-
ing, and coughing, but physical findings during an asthma
exacerbation can be variable. Early symptoms include a sensa-
tion of chest constriction and coughing. As the exacerbation
progresses, wheezing becomes apparent, expiration becomes
prolonged, and use of the accessory respiratory muscles may
become evident. Patients may sit upright or lean forward in
an attempt to decrease the work of breathing. Use of the acces-
sory muscles of inspiration indicates diaphragmatic fatigue,
whereas the appearance of paradoxic respirations reflects
impending ventilatory failure. Alteration in mental status
heralds respiratory arrest.
VARIATIONS IN PRESENTING SIGNS
AND SYMPTOMS
Patients with asthma exacerbations may simply exhibit cough-
ing or have a feeling of chest tightness. At the other end of
the spectrum are patients with a silent chest, which reflects
very severe airflow obstruction and air movement insufficient
to promote a wheeze.
398
A subset of asthmatic patients experience a sudden onset
of severe symptoms. These individuals tend to respond rapidly
to treatment but appear to be at significant risk for a fatal
outcome.6-9
DIFFERENTIAL DIAGNOSIS
Wheezing, coughing, and dyspnea may be cause by many
common conditions, including pneumonia, bronchitis, croup,
bronchiolitis, chronic obstructive pulmonary disease, conges-
tive heart failure, pulmonary embolism, allergic reactions, and
upper airway obstruction from edema or a foreign body. Less
common conditions with similar symptoms are cystic fibrosis,
hypersensitivity pneumonitis, carcinoid syndrome, and expo-
sure to odors, dust, and gas. A careful history and physical
examination should help differentiate asthma from these other
conditions.
DIAGNOSTIC TESTING
As for all patients who come to the ED for care, a directed
history and physical examination should be performed. Key
historical points should be elicited, such as the duration and
onset of the current attack, identification of precipitating
causes, type and amount of medications used before arrival at
the ED, response to previous therapy, including current or
previous use of corticosteroids, frequency of ED visits and
hospitalizations, previous need for intubation or ventilation,
history of concurrent medications and allergies, and history
of concurrent medical problems. At some point during the
patients ED stay, effort should be made to evaluate both the
severity of the obstruction and the adequacy of ongoing
asthma control (Table 48.1).
The physical examination should focus on observing respi-
ratory effort and use of accessory muscles and listening for
wheezing or other abnormal breath sounds and prolongation
of the expiratory phase. Although wheezing results from
movement of air through narrowed airways, the intensity of
the wheeze may not correlate with the severity of airflow
obstruction. Tachycardia and tachypnea are usually present in
patients with acute asthma, but vital signs normalize very
quickly as the airflow obstruction is relieved.10 Therefore, a
normal heart rate and respiratory rate are not reliable indica-
tors of the degree of relief from obstruction.
Bedside spirometry provides a rapid, objective assessment
of patients and helps both indicate the effectiveness of and
guide therapy. Sequential measurements assist emergency
physicians in assessing the severity of the problem and deter-
mining the response to therapy. Although forced expiratory
volume in 1 second (FEV1) and the peak expiratory flow
(PEF) rate measure the extent of large airway obstruction,
patient cooperation is essential for these tests to be reliable.
When possible, management decisions should be guided by a
patients personal best PEF rate or FEV1 value or, if unknown,
a percentage of the predicted value in addition to other physi-
ologic and historical factors.1
Pulse oximetry is a useful and convenient method for
accessing oxygenation and monitoring oxygen saturation
during treatment. Analysis of arterial blood gases is not indi-
cated in the majority of patients with mild to moderate asthma
 CHAPTER 48 Asthma

Table 48.1 Classification of Asthma Severity: Clinical Features Before Treatment

NIGHTTIME
SYMPTOMS SYMPTOMS LUNG FUNCTION

Step 4: Continual symptoms Frequent FEV1 or PEF < 60% of predicted

Severe Limited physical activity value
persistent Frequent exacerbations PEF variability > 30%

Step 3: Daily symptoms >1 time per FEV1 or PEF > 60% but <80% of
Moderate Daily use of inhaled short-acting 2-agonist week predicted value
persistent Exacerbations affecting activity PEF variability > 30%
Exacerbations > 2 times per week; may last days

Step 2: Mild Symptoms > 2 times per week but >1 time per day 3-4 times per FEV1 or PEF 80% of predicted
persistent Exacerbations may affect activity month value
PEF variability 20%-30%

Step 1: Mild Symptoms < 2 times per week 2 times per FEV1 or PEF 80% of predicted
intermittent Asymptomatic and normal PEFR between exacerbations month value
Exacerbations brief (from a few hours to a few days; PEF variability < 20%
intensity may vary)

Adapted from National Institutes of Health, National Heart, Lung and Blood Institute, National Asthma Education and Prevention Program. Expert Panel
Report 3: guidelines for the diagnosis and management of asthma. NIH Publication No. 08-4051. Bethesda, MD: U.S. Department of Health and Human
Services; August 2007.
FEV1, Forced expiratory volume in 1 minute; PEF, peak expiratory flow; PEFR, peak expiratory flow rate.

exacerbation, but it is helpful if there is concern for hypoven-

tilation with carbon dioxide retention and respiratory acidosis.
Patients with the latter problems almost always have clinical
evidence of severe attacks or spirometry demonstrating PEF
or FEV1 less than 25% of the predicted value.11,12 Practitioners
should be aware that a normal or slightly elevated Paco2 (e.g.,
42mm Hg or higher) indicates extreme airway obstruction
and fatigue and may herald the onset of acute ventilatory
failure.11,12
Routine radiography is unnecessary but is indicated if the
possibility of pneumothorax, pneumomediastinum, pneumo-
nia, or other medical conditions is a concern. In up to one
third of asthmatic patients requiring admission, an abnormal-
ity is demonstrated on chest radiographs.13
A routine complete blood cell count is not indicated and
would probably show modest leukocytosis secondary to the
administration of 2-agonist therapy or corticosteroid treat-
ment. In patients taking theophylline before ED evaluation, a
serum theophylline level should be determined. A routine
electrocardiogram is also unnecessary; electrocardiographic
abnormalities noted include right ventricular strain, abnormal
P waves, and nonspecific ST-T wave abnormalities, which
resolve with treatment. Older patients, especially those with
coexisting heart disease, should undergo cardiac monitoring
during treatment. Asthma severity index scores have failed to
predict outcome better than clinical judgment does.
Use of exhaled nitric oxide measurements and other serum
and urine markers for detection of the severity of the asthma
exacerbation is currently under investigation.14-17
TREATMENT
The goal of treatment of acute asthma in the ED is to rapidly
reverse the airflow obstruction with repetitive or continuous
administration of inhaled 2-agonists, ensure adequate oxy-
genation, and relieve inflammation. The National Asthma
RED FLAGS
A silent chest indicates severe obstruction.
Do not wait for arterial blood gas confirmation to aggres-
sively treat ventilatory or respiratory failure.
Listen to the patientthe patient will frequently be able to
assess the severity of the exacerbation.
Education and Prevention Program Expert Panel has devel-
oped guidelines for emergency treatment of asthma (Fig.
48.1),1 as have other organizations around the world. Prehos-
pital treatment with oxygen and 2-agonists is usually initi-
ated. The following types of medications have been shown to
be effective for the treatment of acute asthma: 2-agonists,
anticholinergics, and glucocorticoids (Table 48.2).1 Magne-
sium should be considered in patients with severe obstruction.
Current evidence does not support the use of heliox (helium-
oxygen mixture) or ketamine, even when the aforementioned
medications fail to relieve bronchospasm. Mast cellstabilizing
agents, methylxanthines, and leukotriene modifiers are cur-
rently reserved for maintenance therapy only.
PHARMACEUTICALS
2-Agonist Agents
2-Agonists are the preferred initial rescue medications for
acute bronchospasm. In addition to bronchodilation, these
drugs inhibit the release of mediators and promote mucocili-
ary clearance.1
The most common side effect of 2-agonist drugs is skeletal
muscle tremor. Patients may also experience nervousness,
anxiety, insomnia, headache, hyperglycemia, palpitations,
tachycardia, and hypertension. Despite earlier concerns about
the potential cardiotoxicity of these agents, clinical experi-
ence has not revealed significant problems. Arrhythmias and

399
SECTION V Thoracic and Respiratory Disorders

Initial assessment
History, physical examination (auscultation, use of
accessory muscles, heart rate, respiratory rate, PEF
or FEV, oxygen saturation, and other tests as indicated

FEV, or PEFR 40% (mild to
moderate exacerbation)
Inhaled 2-agonist by metered
dose inhaler or nebulizer, up to
three doses in first hour
Oxygen to achieve O2 saturation
90%
Oral systemic corticosteroids if no
immediate response or if patient
recently took oral systemic
corticosteroid
FEV, or PEFR < 40% (severe exacerbation) Impending or actual respiratory arrest
Inhaled high dose 2-agonist and Intubation and mechanical ventilation
anticholinergic by nebulization every 20 with 100% O2
minutes or continuously for 1 hour Nebulizer 2-agonist and
Oxygen to achieve O2 saturation 90% anticholinergic
Oral systemic corticosteroid Intravenous corticosteroid
Consider adjunct therapies
Repeat assessment
Symptoms, physical examination, PEF, Admit to hospital
O2 saturation, other tests as needed intensive care

Moderate exacerbation Severe exacerbation

FEV1 or PEFR 40-69% predicted/personal best
Physical exam: moderate symptoms
Inhaled short acting 2-agonist every 60
minutes
Systemic corticosteroid
Continue treatment 1-3 hours, provided there
is improvement
FEV or PEFR < 40% predicted/personal best
Physical exam: severe symptoms at rest,
accessory muscle use, chest retraction
History: high-risk patient
No improvement after initial treatment
Inhaled short-acting -agonist, hourly or
continuous + inhaled anticholinergic
Oxygen
Systemic corticosteroid
Consider adjunct therapies

Good response Incomplete response Poor response

FEV1 or PEFR 70%
Response sustained 60 minutes
after last treatment
No distress
Physical exam: normal
FEV1 or PEFR 40-69% FEV1 or PEFR < 40%
Mild to moderate symptoms PCO2 42 mm Hg
Physical exam: symptoms
severe, drowsiness, confusion

Individualized decision regarding

hospitalization (see text)

Discharge home
Continue treatment with
inhaled -agonist
Consider treatment with
inhaled corticosteroids
Continue course of oral
systemic corticosteroid
Patient education
- Review medicine use
- Review/initiate action plan
- Recommend close medical
follow-up
Admit to observation unit or hospital ward
Inhaled 2-agonist
Systemic (oral or intravenous) corticosteroid
Oxygen
Monitor FEV1 or PEF, O2 saturation, pulse
Admit to hospital intensive care
Inhaled 2-agonist hourly or
continuously
Intravenous corticosteroid
Oxygen
Consider adjunct therapies
Possible intubation and mechanical
ventilation

Fig. 48.1 Management of asthma exacerbations: emergency department and hospital-based care. FEV1, Forced expiratory
volume in 1 second; PEF, peak expiratory flow; PEFR, peak expiratory flow rate. (Adapted from National Institutes of Health, National Heart,
Lung and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and
management of asthma. NIH Publication No. 08-4051. Bethesda, MD: U.S. Department of Health and Human Services; August 2007.)

400
 CHAPTER 48 Asthma

Table 48.2 Medications Used to Treat Asthma Exacerbations

DOSAGES

MEDICATION ADULT DOSE CHILD DOSE* COMMENTS

Short-Acting Inhaled 2-Agonists

Albuterol
Nebulizer solution 2.5-5mg every 20min for 0.15mg/kg (minimum dose, 2.5mg) Only selective 2-agonists are
(5.0mg/mL, 3 doses, then every 20min for 3 doses, then recommended
2.5mg/3mL, 2.5-10mg every 1-4hr 0.15-0.3mg/kg up to 10mg For optimal delivery, dilute
1.25mg/3mL, as needed, or every 1-4hr as needed, or aerosols to a minimum of
0.63mg/3mL) 10-15mg/hr 0.5mg/kg/hr by continuous 3mL with gas flow of 6-8L/
continuously nebulization min
MDI (90mcg per puff) 4-8 puffs every 20min up 4-8 puffs every 20min for 3 doses, As effective as nebulized therapy
to 4hr, then every then 1-4hr inhalation maneuver if patient is able to coordinate
1-4hr as needed Use spacer/holding chamber

Bitolterol
Nebulizer solution See albuterol dose See albuterol dose Use has not been studied for
(2mg/mL) Thought to be half as potent as severe asthma exacerbations
albuterol on a milligram basis Do not mix with other drugs
MDI (370mcg per puff) See albuterol dose See albuterol dose Use has not been studied for
severe asthma exacerbation

Levalbuterol (R-albuterol) 1.25-2.5mg every 20min 0.075mg/kg (minimum dose, 0.63mg of levalbuterol is
nebulizer solution for 3 doses, then 1.25mg) every 20min for 3 equivalent to 1.25mg of
(0.63mg/3mL, 1.25-5mg every 1-4hr doses, then 0.075-0.15mg/kg up racemic albuterol in both
1.25mg/3mL) as needed, or to 5mg every 1-4hr as needed, efficacy and side effects
5-7.5mg/hr or 0.25mg/kg/hr by continuous
continuously nebulization

Pirbuterol MDI (200mcg See albuterol dose See albuterol dose Use has not been studied for
per puff) Thought to be half as potent as severe asthma exacerbations
albuterol on a milligram basis

Systemic (Injected) 2-Agonists

Epinephrine 1:1000 0.3-0.5mg every 20min 0.01mg/kg up to 0.3-0.5mg every No proven advantage of
(1mg/mL) for 3 doses SC 20min for 3 doses SC systemic therapy over aerosol

Terbutaline (1mg/mL) 0.25mg every 20min for 0.01mg/kg every 20min for 3 No proven advantage of
3 doses SC doses, then every 2-6hr as systemic therapy over aerosol
needed SC

Anticholinergics

Ipratropium bromide
Nebulizer solution 0.5mg every 30min for 3 0.25mg every 20min for 3 doses, May mix in same nebulizer with
(0.25mg/mL) doses, then every then every 2 to 4hr albuterol
2-4hr as needed Should not be used as first-line
therapy; should be added to
2-agonist therapy
MDI (18mcg per puff) 4-8 puffs as needed 4-8 puffs as needed Dose delivered from MDI is low,
and its use has not been
studied for asthma
exacerbations

Ipratropium with albuterol

Nebulizer solution (each 3mL every 30min for 3 1.5mL every 20min for 3 doses, Contains EDTA to prevent
3-mL vial contains doses, then every then every 2-4hr discoloration
0.5mg ipratropium 2-4hr as needed This additive does not induce
bromide and 90mcg bronchospasm
albuterol)
MDI (each puff contains 4-8 puffs as needed 4-8 puffs as needed
18mcg ipratropium
bromide and 90mcg
albuterol)

Continued

401
SECTION V Thoracic and Respiratory Disorders

Table 48.2 Medications Used to Treat Asthma Exacerbationscontd

DOSAGES

MEDICATION ADULT DOSE CHILD DOSE* COMMENTS

Systemic Corticosteroids

Prednisone, 40-80mg/day in 1 or 2 1mg/kg (maximum, 60mg/day) in 2 For outpatient burst, use

methylprednisolone, divided doses until PEF
prednisolone reaches 70% of
predicted value or
patients personal best
divided doses until PEF reaches
70% of predicted value or
patients personal best
40-60mg in a single dose
or 2 divided doses for adults
(children: 1-2mg/kg/day;
maximum, 60mg/day) for
3-10 days

EDTA, Ethylenediaminetetraacetic acid; MDI, metered dose inhaler; PEF, peak expiratory flow; SC, subcutaneously.
*Children younger than 12 years.
Note: No advantage has been found for higher-dose corticosteroids for severe asthma exacerbations, nor does intravenous administration have any
advantage over oral therapy, provided that gastrointestinal transit time or absorption is not impaired. The usual regimen is to continue the frequent multiple
daily doses until the patient achieves a forced expiratory volume in 1 second or PEF of 50% of the predicted value or the patients personal bestwhich
usually occurs within 48 hoursand then to lower the dosage to twice daily. Therapy after a hospitalization or ED visit may last 3 to 10 days. For
corticosteroid courses lasting 1 week or less, there is no need to taper the systemic corticosteroid dose. For slightly longer courses (e.g., up to 10 days),
there is probably no need to taper, especially if patients are concurrently taking inhaled corticosteroids. If the follow-up systemic corticosteroid therapy is
to be given once daily, one study indicates that it may be more clinically effective to give the dose in the afternoon at 3 PM, with no increase in adrenal
suppression.18

evidence of myocardial ischemia are rare, especially in
patients without a previous history of coronary artery disease.
Aerosol therapy with 2-agonist drugs produces excellent
bronchodilation with minimal systemic absorption and few
side effects. Aerosol delivery may be achieved with a metered
dose inhaler (MDI) with a spacing device or a compressor-
driven nebulizer.19 A spacing device attached to the inhaler
can improve drug deposition when patient technique is inad-
equate. Even with optimal technique only a maximum of 15%
of the dose of the drug is retained in the lungs, regardless of
the aerosol method used. Since 2008, dry-powder delivery
devices and MDIs using hydrofluoroalkane as propellant have
replaced chlorinated fluorocarbondriven devices. Aerosol
treatments may be administered every 15 to 20 minutes or on
a continuous basis.20 Subcutaneous administration of terbuta-
line or epinephrine may be used in patients unable to coordi-
nate aerosolized or MDI treatments or to tolerate aerosolized
medications.21
Intravenous 2-agonist infusions offer no advantage over
aerosolized or MDI-delivered agents and carry potential
risk.22
Salmeterol xinafoate is indicated only as maintenance
therapy, should never be used more frequently than twice
per day, and is to be avoided for the treatment of acute
exacerbations.1
Corticosteroids
Corticosteroids, highly effective drugs for asthma exacerba-
tion, are a cornerstone of treatment.23 They are thought to
produce beneficial effects by restoring 2-agonist responsive-
ness and reducing inflammation. Onset of the antiinflamma-
tory effects of corticosteroids is delayed at least 4 to 8 hours
after intravenous or oral administration.
Data indicate that corticosteroids, administered within 1
hour of arrival in the ED, reduce the need for hospitalization
of a patient with an asthma exacerbation.23 Although evidence
for what constitutes the optimal dose for acute asthma is
lacking, experts agree that an initial 40- to 60-mg dose of
prednisone or an intravenous 60- to 125-mg bolus of methyl-
prednisolone in patients unable to tolerate oral medications is
usually adequate. No advantage has been demonstrated for
higher doses.24 Additional doses should be given every 4 to 6
hours until significant subjective and objective improvement
is achieved. Patients who are being discharged home after
ED treatment should be prescribed a 3- to 10-day nontapering
burst of oral steroids, such as prednisone, 40 to 60mg/day,
or its equivalent.
Current recommendations favor inhaled corticosteroids
for maintenance of all patients with mild persistent asthma or
more severe asthma.1 Therefore, consideration should be
given to discharging any patient with mild persistent or more
severe asthma with maintenance inhaled corticosteroid therapy
in addition to the burst of oral steroids.25
Anticholinergics
Aerosolized ipratropium bromide, 0.5mg, should be admin-
istered to patients with a severe exacerbation of asthma.
Ipratropium is a synthetic quaternary derivative that is avail-
able as both a nebulized solution and in an MDI (18mg per
puff) and is well tolerated (see Table 48.2). Clinical trials
indicate that adding ipratropium to 2-agonist agents offers
mild additional improvement in bronchodilation and signifi-
cantly decreases the need for hospitalization.26 Side effects
include dry mouth, thirst, and difficulty swallowing. Less
commonly, tachycardia, restlessness, irritability, confusion,
difficulty in micturition, ileus, blurring of vision, and an
increase in intraocular pressure are noted.

402

At discharge, addition of tiotropium to the patients current
inhaled corticosteroid dose is comparable to the addition of
salmeterolboth are more effective in achieving disease
control than is doubling the inhaled corticosteroid dose.27
Magnesium
Intravenous magnesium sulfate is indicated for the manage-
ment of acute, very severe asthma, such as a patient with an
FEV1 less than 25% of predicted, but not in those with mild
or moderate asthma exacerbation.28-30 The dose is 1 to 2g
intravenously delivered over a 30-minute period. Inhaled mag-
nesium may also be a helpful adjunct in the treatment of a
severe exacerbation.31,32 Magnesium is not a substitute for
standard therapy regimens.
Heliox, Ketamine, and Halothane
Helium is not indicated for use in patients with mild or moder-
ate asthma exacerbation, although several studies have dem-
onstrated its effectiveness for very severe asthma.33 Several
investigators have reported success with ketamine34,35 and
halothane in patients in whom all other treatment modalities
have failed. Controlled trials substantiating these claims are
lacking.
Mast Cell Modifiers
Neither cromolyn nor nedocromil, both modulators of mast
cell mediator release and eosinophil recruitment, is indicated
for the treatment of acute bronchospasm.
Leukotriene Modifiers
Leukotriene modifiers improve lung function, diminish symp-
toms, and reduce the need for short-acting 2-agonists.1 They
are recommended as an alternative to low-dose inhaled corti-
costeroid therapy in patients with mild persistent asthma
and as steroid-sparing agents with inhaled corticosteroids in
those with moderate persistent asthma. Several leukotriene
modifiersmontelukast, zafirlukast, and zileutonare cur-
rently available as oral tablets for the treatment of asthma.
Although intravenous montelukast has been demonstrated to
cause rapid bronchodilation when used as adjuvant therapy
for acute asthma in a single trial, recommending its use for
the treatment of acute bronchospasm in the ED would be
premature.36 Montelukast, zafirlukast, and zileuton have been
associated with neuropsychiatric side effects.
Theophylline
Although theophylline is no longer considered a first-line
treatment of acute asthma,37 some patients who come to the
ED for treatment may be using it at home. Some data suggest
that this agent has an antiinflammatory mechanism of action.
When used in combination with inhaled 2-agonists, theoph-
ylline appears to increase the toxicitybut not the efficacy
of treatment. The most common side effects of theophylline
are nervousness, nausea, vomiting, anorexia, and headache.
At plasma theophylline levels greater than 30mcg/mL, there
is a risk for seizures and cardiac arrhythmias.
MECHANICAL VENTILATION
When it appears that a patient needs more than the aforemen-
tioned treatments, noninvasive positive pressure ventilation
may be attempted. Data showing that bilevel positive airway
CHAPTER 48 Asthma
pressure reduces the need for intubation and mechanical ven-
tilation are lacking.38-40
If the patient begins to exhibit signs of acute ventilatory
failure with progressive hypercapnia and acidosis or becomes
exhausted or confused, intubation and mechanical ventilation
are needed to prevent respiratory arrest. Mechanical ven
tilation can eliminate the work of breathing and enable the
patient to rest. It does not relieve the airflow obstruction.
Direct, controlled oral intubation by an experienced physician
is preferred.
The potential complications of mechanical ventilation in
asthmatic patients are numerous: barotrauma, hemodynamic
impairment, mucous plugging leading to increased airway
resistance, atelectasis, and pulmonary infection. Air trapp
ing and increased residual volume (intrinsic positive end-
expiratory pressure) may be partially avoided with controlled
mechanical hypoventilation or permissive hypoventilation.39,40
This form of mechanical ventilation is achieved by using a
reduced respiratory rate and low inspiratory volume and pres-
sure and allowing adequate time for the expiratory phase. One
can achieve the goal of ventilatory supportmaintenance of
adequate arterial oxygen saturation (90% or greater)with-
out concern about normalizing the hypercapnic acidosis.
All patients requiring mechanical ventilation should be admit-
ted to an intensive care unit.
PRIORITY ACTIONS
1. Ensure adequate oxygenation.
2. Reverse airflow obstruction with 2-agonists.
3. Relieve inflammation by prescribing oral systemic
corticosteroids.
4. Monitor response to therapy with serial assessments.
DISPOSITION
Disposition decisions for patients after treatment of asthma
exacerbation are rarely straightforward. A number of subjec-
tive and objective factors should be considered, as follows:
Does the patient feel that the wheezing and air exchange
have improved?
Does auscultation confirm improvement or lack thereof?
Has a significant improvement in FEV1 or PEF been noted?
What is the patients health care history?
Is the patient usually compliant with care plans and medica-
tion regimens?
Does the patient have access to prompt follow-up?
Does the patient usually require hospitalization after an
exacerbation?
Unfortunately, a formula for successful discharge without risk
for early relapse does not yet exist, and up to 25% of patients
treated in the ED for asthma return within 3 weeks.41-44
Because some degree of residual airflow obstruction,
airway lability, and inflammation persists after treatment and
discharge from the ED, a postdischarge treatment plan must
be formulated.
403
SECTION V Thoracic and Respiratory Disorders

Addition of a short, nontapering course of oral steroids to

the scheduled use of a 2-agonist bronchodilator reduces DOCUMENTATION
relapse rates in discharged patients. Patients with chronic
asthma who are not using controller medications at home
History
should be prescribed and educated about the daily use of
Asthma control and severity
either inhaled corticosteroids or leukotriene modifiers, in
Previous severe exacerbations (need for intubation or inten-
addition to their rescue medications.45 Data indicate that
sive care unit admission)
relying on the primary care physician to prescribe these con-
Risk factors:
trollers at follow-up is inadequate.25
Two or more hospitalizations or more than three emer-
Current guidelines suggest that patients with a good
gency department visits in the past year
response to treatment, as demonstrated by complete resolution
Use of more than two canisters of short-acting -agonists
of symptoms and a PEF or FEV1 value greater than 70%
per month
of predicted, can be safely discharged home. Patients with a
Poor perception of bronchospasm
poor response to treatment, as defined by persistent symp-
Medication noncompliance
toms, a PEF or FEV1 value less than 50% of predicted, and
Illicit drug use
persistent wheezing and dyspnea at rest, should be admitted.
Major psychosocial problems or psychiatric disease
Many patients with an incomplete response to treatment, as
Comorbid conditions, such as cardiovascular disease or
defined by some persistence of symptoms and a PEF or FEV1
other chronic lung disease
value between 50% and 70% of predicted, may be discharged
home safely, provided that they have no risk factors for death Examination
from asthma.1 Patients who do not show adequate improve- Vital signs and oxygen saturation
ment over several hours because they are in the late phase Cardiopulmonary examination
of the exacerbation and those with significant risk factors Emergency Department Course
for death from asthma should be admitted to either an obser- Monitor response to therapy with serial assessments
vation unit or the hospital. Most patients have an incomplete
response to treatment and fall into this gray zone of disposi-
tion decisions.
Studies indicate that the majority of asthmatic patients SUGGESTED READINGS
admitted to an observation unit where strict care protocols are National Institutes of Health, National Heart, Lung and Blood Institute, National
followed can be successfully treated and discharged.45 Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for
Early follow-up care is indicated to monitor resolution of the diagnosis and management of asthma. NIH Publication No. 084051. Bethesda,
the exacerbation and to review the long-term medication and MD: U.S. Department of Health and Human Services; August 2007.
Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children and
care plans for the ongoing management of asthma. High adults with acute asthma: a systematic review with meta-analysis. Thorax
relapse rates despite the routine use of steroids strongly 2005;60:740-6.
suggest the need for follow-up within days of the ED visit. Rowe BH, Spooner C, Ducharme FM, et al. Early emergency department treatment of
Ideally, education of the patient begins in the ED, and a written acute asthma with systemic corticosteroids. Cochrane Database Syst Rev
2001;1:CD002178.
plan of action that addresses both routine treatment and care Rowe BH, Spooner CH, Ducharme FM, et al. Corticosteroids for preventing relapse
of worsening symptoms is developed either in the ED or following acute exacerbations of asthma (Cochrane Review). In: The Cochrane
at follow-up. ED personnel should provide basic education Library. Oxford: Update Software; 2004.
about asthma and help connect the patient with a primary
care provider or asthma specialist while providing discharge
instructions. Review of the patients discharge medication, REFERENCES
evaluation of inhaler technique, and instruction on the use of
peak flow monitoring are just some of the issues that emer- References can be found on Expert Consult @
gency physicians can teach and emphasize. www.expertconsult.com.

404

REFERENCES
1. National Institutes of Health, National Heart, Lung and Blood Institute, National
Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for
the diagnosis and management of asthma. NIH Publication No. 084051.
Bethesda, MD: U.S. Department of Health and Human Services; August 2007.
2. National Center for Health Statistics. Health, United States. Hyattsville, MD:
Public Health Service; 2000.
3. Moorman JE, Rudd RA, Johnson CA, et al. MMWR Surveillance Summaries.
National Surveillance for AsthmaUnited States, 1980-2004. Centers for Disease
Control and Prevention. Available at http://www.cdc.gov/mmwr/preview/
mmwrhtml/ss5608.al.htm.
4. Barnett SB, Nurmagambetov TA. Costs of asthma in the United States:
2002-2007. J Allergy Clin Immunol 2011;127:145-52.
5. Bousquet J, Jeffery PK, Busse WW, et al. Asthma: from bronchoconstriction to
airways inflammation and remodeling. Am J Respir Crit Care Med
2000;161:1720-45.
6. Robin ED. Unexpected, unexplained sudden death in young asthmatic subjects.
Chest 1989;96:790-3.
7. Wasserfallen JB. Sudden asphyxic asthma: a distinct entity? Am Rev Respir Dis
1990;142:108-11.
8. Brooks SM, Hammad Y, Richards I, et al. The spectrum of irritant-induced
asthma: sudden and not-so-sudden onset and the role of allergy. Chest
1998;113:42-9.
9. Barr RG, Woodruff PG, Clark S, et al. Sudden-onset asthma exacerbations:
clinical features, response to therapy, and 2-week follow-up. Multicenter Airway
Research Collaboration (MARC) investigators. Eur Respir J 2000;15:266-73.
10. Carden DL, Nowak RM, Sarkar D, et al. Vital signs including pulsus paradoxus in
the assessment of acute bronchial asthma. Ann Emerg Med 1983;12:80-3.
11. Martin TG, Elenbaas RM, Pingleton SH. Use of peak expiratory flow rates to
eliminate unnecessary arterial blood gases in acute asthma. Ann Emerg Med
1982;11:70-3.
12. McFadden Jr ER. Clinical physiologic correlates in asthma. J Allergy Clin
Immunol 1986;77:1-5.
13. White CS. Acute asthma: admission chest radiography in hospitalized adult
patients. Chest 1991;100:14-6.
14. Shome GP, Starnes JD, Shearer M, et al. Exhaled nitric oxide in asthma:
variability, relation to asthma severity, and peripheral blood lymphocyte cytokine
expression. J Asthma 2006;43:95-9.
15. Redington AE. Modulation of nitric oxide pathways: therapeutic potential in
asthma and chronic obstructive pulmonary disease. Eur J Pharmacol
2006;533:263-76.
16. Taylor DR. Nitric oxide as a clinical guide for asthma management. J Allergy
Clin Immunol 2006;117:259-62.
17. Spergel JM, Fogg MI, Bokszczanin-Knosala A. Correlation of exhaled nitric
oxide, spirometry and asthma symptoms. J Asthma 2005;42:879-83.
18. Beam WR, Weiner DE, Martin RJ. Timing of prednisone and alterations of
airways inflammation in nocturnal asthma. Am Rev Respir Dis
1992;146:1524-30.
19. Cates CJ, Rowe BH. Holding chambers versus nebulisers for beta-agonist
treatment of acute asthma. Cochrane Database Syst Rev 2000;2:CD000052.
20. Camargo Jr C, Spooner C, Rowe B. Continuous versus intermittent beta-agonists
in the treatment of acute asthma. Cochrane Database Syst Rev 2003;4:CD001115.
21. Cydulka R, Davison R, Grammer L, et al. The use of epinephrine in the treatment
of older adult asthmatics. Ann Emerg Med 1988;17:322-6.
22. Travers A, Jones AP, Kelly K, et al. Intravenous beta2-agonists for acute asthma
in the emergency department. Cochrane Database Syst Rev 2001;2:CD002988.
23. Rowe BH, Spooner C, Ducharme FM, et al. Early emergency department
treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst
Rev 2001;1:CD002178.
CHAPTER 48 Asthma
24. Emerman CL, Cydulka RK. A randomized comparison of 100-mg vs 500-mg
dose of methylprednisolone in the treatment of acute asthma. Chest
1995;107:1559-63.
25. Cydulka RK, Tamayo-Sarver JH, Wolf C, et al. Inadequate follow-up controller
medications among patients with asthma who visit the emergency department.
Ann Emerg Med 2005;46:316-22.
26. Rodrigo GJ, Castro-Rodriguez JA. Anticholinergics in the treatment of children
and adults with acute asthma: a systematic review with meta-analysis. Thorax
2005;60:740-6.
27. Peters SP, Kunselman SJ, Icitovic N, et al, for the National Heart, Lung, and
Blood Institute Asthma Clinical Research Network. Tiotropium bromide step-up
therapy for adults with uncontrolled asthma. N Engl J Med 2010;363:1715-26.
28. Rowe BH, Camargo Jr CA. The use of magnesium sulfate in acute asthma: rapid
uptake of evidence in North American emergency departments. J Allergy Clin
Immunol 2006;117:53-8.
29. Silverman RA, Osborn H, Runge J, et al. IV magnesium sulfate in the treatment
of acute severe asthma: a multicenter randomized controlled trial. Chest
2002;122:489-97.
30. Cheuk DK, Chau TC, Lee SL. A meta-analysis on intravenous magnesium
sulphate for treating acute asthma. Arch Dis Child 2005;90:74-7.
31. Kokturk N, Turktas H, Kara P, et al. A randomized clinical trial of magnesium
sulphate as a vehicle for nebulized salbutamol in the treatment of moderate to
severe asthma attacks. Pulm Pharmacol Ther 2005;18:416-21.
32. Blitz M, Blitz S, Hughes R, et al. Aerosolized magnesium sulfate for acute
asthma: a systematic review. Chest 2005;128:337-44.
33. Rodrigo GJ, Rodrigo C, Pollack CV, et al. Use of helium-oxygen mixtures in the
treatment of acute asthma: a systematic review. Chest 2003;123:891-6.
34. Howton JC. Randomized, double-blind, placebo-controlled trial of intravenous
ketamine in acute asthma. Ann Emerg Med 1996;27:170-5.
35. Lau TT, Zed PJ. Does ketamine have a role in managing severe exacerbation of
asthma in adults? Pharmacotherapy 2001;21:1100-6.
36. Camargo Jr CA, Smithline HA, Malice MP, et al. A randomized controlled trial of
intravenous montelukast in acute asthma. Am J Respir Crit Care Med
2003;167:528-33.
37. Parameswaran K, Belda J, Rowe BH. Addition of intravenous aminophylline to
beta2-agonists in adults with acute asthma. Cochrane Database Syst Rev
2000;4:CD002742.
38. Soroksky A, Stav D, Shpirer I. A pilot prospective, randomized, placebo-
controlled trial of bilevel positive airway pressure in acute asthmatic attack. Chest
2003;123:1018-25.
39. Oddo M, Feihl F, Schaller MD, et al. Management of mechanical ventilation in
acute severe asthma: practical aspects. Intensive Care Med 2006;32:501-10.
40. Austan F, Polise M. Management of respiratory failure with noninvasive positive
pressure ventilation and heliox adjunct. Heart Lung 2002;31:214-8.
41. Rowe BH, Spooner CH, Ducharme FM, et al. Corticosteroids for preventing
relapse following acute exacerbations of asthma (Cochrane Review). In: The
Cochrane Library. Oxford: Update Software; 2004.
42. Emerman CL, Cydulka RK, Crain EF, et al. Prospective multicenter study of
relapse after treatment for acute asthma among children presenting to the
emergency department. J Pediatr 2001;138:318-24.
43. Emerman CL, Woodruff PG, Cydulka RK, et al. Prospective multicenter study of
relapse following treatment for acute asthma among adults presenting to the
emergency department. MARC investigators. Multicenter Asthma Research
Collaboration. Chest 1999;115:919-27.
44. Frey U. Predicting asthma control and exacerbations: chronic asthma as a
complex dynamic model. Curr Opin Allergy Clin Immunol 2007;7:223-30.
45. Rydman RJ, Isola ML, Roberts RR, et al. Emergency department observation unit
versus hospital inpatient care for a chronic asthmatic population: a randomized
trial of health status outcome and cost. Med Care 1998;36:599-609.
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