Status Asthmaticus

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Background: Status asthmaticus is a medical emergency in Center
which asthma symptoms are refractory to initial
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bronchodilator therapy in the emergency department. Articles
Patients report chest tightness, rapidly progressive shortness
of breath, dry cough, and wheezing. Typically, patients Asthma CME
present a few days after the onset of a viral respiratory
illness, following exposure to a potent allergen or irritant, or Asthma Multimedia
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after exercise in a cold environment. Frequently, patients
have underused or have been underprescribed anti-
inflammatory therapy. Illicit drug use may play a role in poor
adherence to anti-inflammatory therapy. Patients may have
increased their beta-agonist intake (either inhaled or Quick Find
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Introduction
Pathophysiology: Inflammation in asthma is characterized Clinical
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and a mixed cellular infiltrate composed of eosinophils, mast Treatment
cells, lymphocytes, and neutrophils during the late-phase (or Medication
chronic) reaction. The simple explanation for allergic Follow-up
inflammation in asthma begins with the development of a Miscellaneous
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predominantly helper T2 lymphocyte–driven, as opposed to
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caused by certain types of immune stimulation early in life. images.
This is followed by allergen exposure in a genetically
susceptible individual. Specific allergen exposure (eg, dust
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elaboration and release of a vast array of mediators. These
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and a host of cytokines. Together, these mediators cause
bronchial smooth muscle constriction, vascular leakage, Asthma Center
inflammatory cell recruitment (with further mediator release),
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and mucous gland secretion. These processes lead to
airway obstruction by constriction of the smooth muscles, Asthma Causes
edema of the airways, influx of inflammatory cells, and
formation of intraluminal mucus. In addition, ongoing airway Asthma Symptoms
inflammation is thought to cause the airway hyperreactivity
characteristic of asthma. The more severe the airway Asthma Treatment
obstruction, the more likely ventilation-perfusion mismatching
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will result in impaired gas exchange and hypoxemia.
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Frequency: Asthma Medications

• In the US: The prevalence and severity of asthma

cases are on the rise (see Asthma). Also increasing
are the occurrences of asthma hospitalization and
mortality resulting from status asthmaticus. Status
asthmaticus is usually more common among persons
in low socioeconomic groups, regardless of race, and
particularly in people who live alone.

• Internationally: Similar to the US data, asthma

mortality rates are increasing.

Mortality/Morbidity:

• Patients who delay medical treatment, particularly

treatment with systemic steroids, have a greater
chance of dying.

• Patients with other preexisting conditions (eg,

restrictive lung disease, congestive heart failure, chest
deformities) are at particular risk of death from status
asthmaticus.

• Patients who smoke regularly have chronic

inflammation of the small airways and are at particular
risk of death from status asthmaticus.
Race:

• A recent study by Hanania et al noted that although

asthma is more common among African American
and Hispanic persons, this prevalence may be the
result of socioeconomic factors rather than race.

• African American and Hispanic persons in the United

States, in association with lower socioeconomic
factors, have less access to regular specialist medical
care, which leads to an increased risk of status
asthmaticus.

• In the United States, particularly in large cities,

illiteracy and lower educational competence are more
prevalent in African American and Hispanic families,
and children in these families have increased
morbidity from asthma.

Sex:

• Status asthmaticus is slightly more common in males

than in females.

Age:

• Status asthmaticus can occur in persons of any age

group, including infants and geriatric patients.
Mortality rates are higher in very young children and
elderly adults.

• Children younger than 2 years, and sometimes those

older, may have respiratory syncytial virus (RSV)
infections that can result in severe attacks of
wheezing that mimic status asthmaticus. Also, RSV
infections can predispose patients to asthma later in
life.

CLINICAL Section 3 of 10
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History:
 • Patients with status asthmaticus have severe dyspnea
that has developed over hours to days.

• Frequently, patients have a prior history of

endotracheal intubation and mechanical ventilation,
frequent emergency department visits, and previous
use of systemic corticosteroids.

• Patients usually present with audible wheezing.

Physical:

• Patients are usually tachypneic upon examination

and, in early stages of status asthmaticus, may have
significant wheezing. Initially, wheezing is heard only
during expiration, but, later, wheezing occurs during
both expiration and inspiration.

• The chest is hyperexpanded, and accessory muscles,

particularly the sternocleidomastoid, scalene, and
intercostal muscles, are used. Later, as
bronchoconstriction worsens, patients' wheezing may
disappear, which may indicate severe airflow
obstruction.

• Normally, the pulsus paradoxus (ie, the difference in

systolic blood pressure between inspiration and
expiration) does not exceed 15 mm Hg. In patients
with severe asthma, a pulsus paradoxus of greater
than 25 mm Hg usually indicates severe airway
obstruction.

Causes:

• In persons with acute asthma, bronchospasms occur

as a result of one or more inciting factors that may
include, but are not limited to, a viral upper or lower
respiratory tract infection, significant allergic response
to an allergen (eg, pollen, mold, animal dander, house
dust mites), exposure to an irritant, or vigorous
exercise in a cold environment.

• Precipitating factors can include infection, allergen or

irritant exposure, poor adherence to the medical
regimen, strenuous exercise, and a rapid decrease in
 long-term oral steroid therapy.

• Inflammation can be the result of infection;

lymphocyte, mast cell, eosinophilic, and neutrophilic
responses; and airway epithelial damage.

DIFFERENTIALS Section 4 of 10
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Pulmonary Hypertension, Primary

Other Problems to be Considered:

Congestive heart failure

Croup
Stridor
Upper airway obstruction
Orthopnea

WORKUP Section 5 of 10
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Lab Studies:

• Obtain a CBC count and differential to evaluate for infectious causes (eg,
pneumonia, viral infections such as croup), allergic bronchopulmonary
aspergillosis, and Churg-Strauss vasculitis.

• Obtain an arterial blood gas (ABG) value to assess the severity of the asthma
attack and to substantiate the need for more intensive care. ABG
determinations are indicated when the peak expiratory flow (PEF) rate or
forced expiratory volume in one second (FEV1) is less than or equal to 30% of
the predicted value or when the patient shows evidence of fatigue or
progressive airway obstruction despite treatment. ABG values are important
to help determine the severity of the asthma attack. The 4 stages of blood
gas progression in persons with status asthmaticus are as follows:

o The first stage is characterized by hyperventilation with a normal

partial pressure of oxygen (PO2).

o The second stage is characterized by hyperventilation accompanied

by hypoxemia (ie, a low partial pressure of carbon dioxide [PCO 2] and
 low PO2).

o The third stage is characterized by the presence of a false-normal

PCO2; ventilation has decreased from the hyperventilation present in
the second stage. This is an extremely serious sign of respiratory
muscle fatigue that signals the need for more intensive medical care,
such as admission to the ICU and, probably, intubation with
mechanical ventilation.

o The last stage is characterized by a low PO2 and a high PCO2, which
occurs with respiratory muscle insufficiency. This is an even more
serious sign that mandates intubation and ventilatory support.

Imaging Studies:

• Obtain a chest radiograph to evaluate for pneumonia, pneumothorax,

congestive heart failure, and signs of chronic obstructive pulmonary disease,
which would complicate the patient's response to treatment or reduce the
patient's baseline spirometry values.

Other Tests:

• The most important and readily available test to evaluate the severity of an
asthma attack is the measurement of PEF. PEF monitors are commonly
available to patients for use at home, and they provide patients with asthma
with a guideline for changes in lung function as they relate to changes in
symptoms. In most patients with asthma, a decrease in peak flow as a
percent of predicted value correlates with changes in spirometry values.

• According to the guidelines of the National Heart, Lung, and Blood

Institute/National Asthma Education and Prevention Program, severe asthma
exacerbation is usually associated with a PEF rate or FEV1 of less than 50%
of the predicted value. Also, hospitalization is generally indicated when the
PEF or FEV1 after treatment is greater than 50% of the predicted value but
less than 70% of the predicted value. Hospitalization in the ICU is indicated
when the PEF value or FEV1 is less than 50% of predicted.

• A drop in the FEV1 to less than 25% of the predicted value indicates a severe
airway obstruction.

• A patient with an FEV1 of greater than 60% of the predicted value may be
treated in an outpatient setting, depending on the clinical situation. However,
if the patient's FEV1 or PEF rate drops to less than 50% of predicted,
admission to the hospital is recommended.

• Pulse oximetry and spirometry values should be used to monitor the

 progression of asthma. As the results indicate improvement, treatment may
be adjusted accordingly.

o If a portable spirometry unit is not available, a PEF rate of 20% or less

of the predicted value (ie, usually <100 L/min) suggests severe airflow
obstruction and impending respiratory failure.

o Spahn et al demonstrate that the majority of children with asthma have

normal spirometry results. According to Goldman et al and Marotta et
al, the assessment of children with asthma is enhanced by the use of
forced oscillation to measure respiratory resistance and reactance. As
reported by Ducharme and Davis in 1997 and 1998, forced oscillation
can be performed in the emergency department, and the results are
reproducible.

o According to various articles, impulse oscillometry resistance and

reactance magnitudes have been shown to be more sensitive than
FEV1 to the daily variability in adolescents with asthma (Goldman et
al), to the response to acute bronchodilation (Marotta et al and Skloot
et al), and to the response to exposure to toxic inhalants in persons
with reactive airways (Skloot et al). In patients with reactive airways,
Saadeh et al report that impulse oscillometry detects false-negative
spirometry values and provides a sensitive index of asthma control
over the spectrum of mild-to-severe persistent asthma.

Procedures:

• With forced oscillation testing using the impulse oscillometry system (IOS),
patients are tested for 30-40 seconds during quiet breathing, without forced
respiratory efforts. A small loudspeaker pushes “burps” of air into patients
and pulls them back from the mouthpiece 5 times each second.

o The measurement of airflow resistance during normal breathing

requires no maximal forced expiratory efforts and does not subject
patients to bronchoprovocation from forced expiration. Resistance is
distributed between large airways and smaller more peripheral
airways, with distinct patterns attributable to each.

o Bronchospasms and increased large airway resistance appear as

increases in resistance at higher (25-35 cycles/s) components of
oscillation frequency. Additionally, a pattern of increased resistance
with increasing airflow is typical of a large airway bronchospasm. In
such patients, resistance at the beginning and end of both inspiration
and expiration is at its minimum, with increased levels during mid
inspiration and mid expiration. In such patients, a deep inspiration is
often followed by reflex bronchoconstriction and increased resistance
 for 30 seconds or more, signaling increased airway reactivity.

o Peripheral airway inflammation and obstruction are signaled by

increased resistance at low (5 cycles/s) oscillation frequencies that are
decreased at higher oscillation frequencies (15 or 20 cycles/s). In
association with the fall in resistance from 5 to 15 cycles per second,
the magnitude of respiratory reactance in peripheral airway
inflammation and obstruction increases.

o Careful attention must be paid to whether patients have their lips fully
closed around the mouthpiece. Patients with acute dyspnea may feel
constrained breathing through a mouthpiece and may reflexively open
their mouths to increase airflow during late inspiration. This is
analogous to flaring alae nasi with dyspnea and results in
characteristic airflow leak patterns. This causes underestimation of
true airflow resistance. IOS tests with such airflow leak patterns must
be repeated after reassuring the patient and ensuring closure of the
lips around the mouthpiece.

Histologic Findings: Autopsy results from patients who died from status
asthmaticus of brief duration (ie, developed within hours) show neutrophilic
infiltration of the airways. In contrast, results from patients who developed status
asthmaticus over days show eosinophilic infiltration. Autopsy results also show
extensive mucus production and severe bronchial smooth muscle hypertrophy.
However, the predominant response, based on results from bronchoalveolar lavage
studies, is eosinophilic in nature. The eosinophil itself can lead to epithelial
destruction through its own degrading products (eg, cationic proteins). This
destruction can result in inflammation and, later, a neutrophilic response.

Staging: The 4 stages of status asthmaticus are based on ABG progressions in

status asthma.

Patients in stage 1 or 2 may be admitted to the hospital, depending on the severity

of their dyspnea, their ability to use accessory muscles, and their PEF values or
FEV1 after treatment (>50% but <70% of predicted values).

Patients with ABG determinations characteristic of stages 3 and 4 require admission

to the ICU. The PEF value or FEV1 is less than 50% of the predicted value after
treatment.

• Stage 1

o Patients are not hypoxemic, but they are hyperventilating and have a
normal PO2.

o Recent data suggest that to possibly facilitate hospital discharge,

 these patients may benefit from ipratropium treatment via a handheld
nebulizer in the emergency setting as an adjunct to beta-agonists.

• Stage 2

o This stage is similar to stage 1, but patients are hyperventilating and

hypoxemic.
o Such patients may still be discharged from the emergency department,
depending on their response to bronchodilator treatment, but will
require systemic corticosteroids.

• Stage 3

o These patients are generally ill and have a normal PCO 2 due to
respiratory muscle fatigue. Their PCO2 is considered a false-normal
value and is a very serious sign of fatigue that signals a need for
expanded care. This is generally an indication for elective intubation
and mechanical ventilation, and these patients require admission to
the ICU.
o Parenteral corticosteroids are indicated, as is continued aggressive
use of an inhaled beta2-adrenergic bronchodilator.
o These patients may benefit from theophylline.

• Stage 4

o This is a very serious stage in which the PO2 is low and the PCO2 is
high, signifying respiratory failure.

o These patients have less than 20% lung function or FEV1 and require
intubation and mechanical ventilation.
o Patients in stage 4 should be admitted to the ICU. Switching from
inhaled beta-2 agonists and anticholinergics to metered-dose inhalers
(MDIs) via mechanical ventilator tubing is indicated.
o Parenteral steroids are essential, and theophylline may be added, as
with patients in stage 3.

TREATMENT Section 6 of 10
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Medical Care: After confirming the diagnosis and assessing the severity of the
asthma attack, direct treatment toward controlling bronchoconstriction and
inflammation.

• Bronchodilator treatment with beta-2 agonists

o The first line of therapy is bronchodilator treatment with a beta-2
 agonist, typically albuterol.
o Handheld nebulizer treatments may be administered either
continuously (10-15 mg/h) or by frequent timing (eg, q5-20min),
depending on the severity of the bronchospasm.
o The dose of albuterol for intermittent dosing is 0.3-0.5 mL of a 0.5%
formulation mixed with 2.5 mL of normal saline. Many of these
preparations are available in a premixed form with a concentration of
0.083%.
o Studies have also shown an excellent response to well-supervised use
of albuterol via an MDI with a chamber. The dose is 4 puffs, repeated
at 15- to 30-minute intervals as needed. Most patients respond within
1 hour of treatment.
o Recently, the US Food and Drug Administration approved the use of
the R isomer of albuterol known as levalbuterol, for treating patients
with acute asthma. This isomer has fewer effects on the heart rhythm
(ie, tachyarrhythmia) and is associated with fewer occurrences of
tremors, while having the same or greater clinical bronchodilator
effects as racemic albuterol.
o The decreased prevalence of adverse effects with this new medication
may allow physicians to use nebulizer therapy in patients with acute
asthma more frequently with less concern over the adverse effects of
other bronchodilators (eg, albuterol, metaproterenol). The dose of
levalbuterol is either a 0.63-mg vial for children or a 1.26-mg vial for
adults.
o These drugs, especially albuterol, are safe to use during pregnancy.

• Nonselective beta-2 agonists

o Patients whose bronchoconstriction is resistant to continuous
handheld nebulizer treatments with traditional beta-2 agonists may be
candidates for nonselective beta-2 agonists (eg, epinephrine [0.3-0.5
mg] or terbutaline [0.25 mg]) administered subcutaneously. However,
systemic therapy has no proven advantage over aerosol therapy with
selective beta-2 agents.
o Exercise caution in patients with other complicating factors (eg,
congestive heart failure, history of cardiac arrhythmia).
o Intravenous isoproterenol is not recommended for the treatment of
asthma because of the risk of myocardial toxicity.

• Ipratropium treatment
o Ipratropium, which comes in premixed vials at 0.2%, can be synergistic
with albuterol or other beta-2 agonists.
o Ipratropium is administered every 4-6 hours.
o Because children appear to have more cholinergic receptors, they are
more responsive to parasympathetic stimulation than adults.

• Oxygen monitoring
 o Monitoring the patient's oxygen saturation is essential during the initial
treatment.
o ABG values are usually used to assess hypercapnia during the
patient's initial assessment.
o Oxygen saturation is then monitored via pulse oximetry throughout the
treatment protocol.
• Oxygen therapy
o Oxygen therapy is essential. It can be administered via a nasal canula
or mask, although patients with dyspnea often do not like masks.
o With the advent of pulse oximetry, oxygen therapy can be easily
titrated to maintain the patient's oxygen saturation above 92% (>95%
in pregnant patients or those with cardiac disease).

• Glucocorticosteroids
o Steroids are the most important treatment for status asthmaticus.
o The usual dose is oral prednisone at 1-2 mg/kg/d.
o In the authors' experience, methylprednisolone provides excellent
efficacy when given intravenously at 1 mg/kg/dose every 6 hours.
o Some authorities report that pulse therapy with steroids at a high dose
(eg, 10-30 mg/kg/d as a single dose) is associated with a more rapid
response and shorter hospitalization and has similar adverse effects;
however, this is not standard therapy. Adverse effects of pulse
therapy, in the authors' experiences, are minimal and comparable to
the traditional doses of intravenous steroids. The adverse effects may
include hyperglycemia, which is usually reversible once steroid therapy
is stopped; increased blood pressure; weight gain; increased striae
formation; and hypokalemia. Long-term adverse effects depend on the
duration of steroid therapy after the patient leaves the hospital.
o Steroid treatment for acute asthma is necessary but has potential
adverse effects. The serum glucose value must be monitored, and
insulin can be administered on a sliding scale if needed. Monitoring a
patient's electrolyte levels, especially potassium, is essential.
Hypokalemia can cause muscle weakness, which may worsen
respiratory distress and cause cardiac arrhythmias.
• Nebulized steroids
o The use of nebulized steroids for treating status asthmaticus is
controversial. Recent data comparing nebulized budesonide with
prednisone in children suggest that the latter therapy is more effective
for treating status asthmaticus.
o No good scientific evidence supports using nebulized dexamethasone
or triamcinolone via a handheld nebulizer. In fact, in the authors'
experiences, more adverse effects, including a cushingoid appearance
and irritative bronchospasms, have occurred with these nebulizers.
• Fluid replacement: Intravenous fluids are administered to restore euvolemia.
• Antibiotics
o The routine administration of antibiotics is discouraged.
 o Patients are administered antibiotics only when they show evidence of
infection (eg, pneumonia, sinusitis).

• Aminophylline
o Conflicting reports on the efficacy of aminophylline therapy have made
it controversial.
o Starting intravenous aminophylline may be reasonable in patients who
do not respond to medical treatment with bronchodilators, oxygen,
corticosteroids, and intravenous fluids within 24 hours.
o Recent data suggest that aminophylline may have an anti-
inflammatory effect in addition to its bronchodilator properties.
o The loading dose is usually 5-6 mg/kg, followed by a continuous
infusion of 0.5-0.9 mg/kg/h.
o Physicians must monitor a patient's theophylline level. Traditionally,
the level was targeted to the higher end of the local therapeutic range;
however, many authorities suggest that the lower portion of the range
(ie, >5 but <10) may be preferable if the patient can obtain the benefits
of the drug in the lower range.
o Adverse effects can include tachyarrhythmia, nausea, seizures, and
anxiety.

Section 7
MEDICATION of
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Beta-agonists, steroids, and theophylline are mainstays in the treatment of status

asthmaticus.

The usual first line of therapy is bronchodilator treatment with a beta-2 agonist,
typically albuterol. This therapy may initially include handheld nebulizer
treatments, either continuously or at frequent intervals (ie, q5-10min), depending
on the severity of the bronchospasm. Most patients respond within 1 hour of
treatment. Recently, the Food and Drug Administration approved the use of
levalbuterol (ie, the R isomer of albuterol) to treat patients with acute asthma.
The advantage of levalbuterol is that it has fewer effects on the patient's heart
rhythm (ie, tachyarrhythmia) and is associated with a less frequent occurrence of
tremors. Levalbuterol has the same clinical bronchodilator effect as racemic
albuterol.
Corticosteroids are essential in the treatment of patients with status asthmaticus.
The mechanism of action of corticosteroids can include a decrease in mucus
production, an improvement in oxygenation, a reduction in beta-agonists or
theophylline requirements, and the activation of properties that may prevent late
bronchoconstrictive responses to allergies and provocation. Corticosteroids can
decrease bronchial hypersensitivity, reduce the recovery of eosinophils and mast
cells in bronchioalveolar lavage fluid, and decrease the number of activated
lymphocytes. Corticosteroids also help regenerate the bronchial epithelial cells.

The exact mode of corticosteroid action is not well understood. Their anti-
inflammatory effect depends, at least partially, on inhibiting phospholipase A2,
which can lead to prostaglandin inhibition and leukotriene synthesis.
Corticosteroid action usually requires at least 4-6 hours from administration
because it requires protein synthesis before it initiates anti-inflammatory effects.
Because of this, patients with status asthmaticus must depend on other
supportive measures (eg, beta-2 agonists, oxygen, adequate ventilation) in their
initial treatment while awaiting the action of corticosteroids.

Theophylline preparations are also used in patients with status asthmaticus.

Usually, theophylline is given parenterally, but it can also be given orally,
depending on the severity of the attack and the patient's ability to take
medications. This class of drugs can induce tachycardia and decrease the
seizure threshold (especially in children); therefore, therapeutic monitoring is
mandatory.

Typical theophylline levels range from 10-20 mcg/mL; however, adverse effects
can occur even with therapeutic levels. A safer range is 10-15 mcg/mL, although
seizures have occurred even with levels below 10 mcg/mL. Theophylline also
has significant drug interactions with medications such as ciprofloxacin, digoxin,
and warfarin (Coumadin). These interactions may decrease the rate of
theophylline clearance by interfering with P-450 site metabolism. On the other
hand, phenytoin (Dilantin) and cigarette smoking can increase the rate of
metabolism of theophylline and, therefore, can decrease the therapeutic level of
the drug.

Manage the theophylline dose in persons who previously smoked but quit fewer
than 6 months ago as if they are still smoking. Patients who smoke or those on
phenytoin require higher loading and maintenance doses of theophylline. Other
adverse effects can include nausea, vomiting, and palpitations.

The usual loading dose of theophylline is 6 mg/kg, followed by maintenance

doses of 1 mg/kg/h in the emergent setting. In patients who smoke, the
maintenance dose may be higher and the loading dose may be slightly higher.
Patients on phenytoin should also receive increased maintenance doses of
theophylline. Patients with liver disease or elderly patients may require a
maintenance dose as low as 0.25 mg/kg/h.
Theophylline can induce bronchodilation, stimulate the central respiratory cycle,
reduce diaphragmatic muscle fatigue, and relax vascular smooth muscles. The
mechanism of action includes an increased cyclic adenosine monophosphate
concentration by the inhibition of phosphodiesterase; however, this usually
occurs when the concentration of theophylline is toxic. Therefore, the true
mechanism of action of theophylline is still unclear, but a possible explanation for
the bronchodilatation may be related to adenosine antagonism. Theophylline is
available in multiple preparations, both short- and long-acting. For patients with
status asthmaticus, short-acting preparations are preferred; however, parental
preparations are even better.

The addition of the anticholinergic ipratropium, which comes in premixed vials at

0.2%, sometimes results in additional bronchodilation beyond that achieved with
albuterol.

Drug Category: Beta-adrenergic agonists -- Relieve reversible

bronchospasm by relaxing smooth muscles of the bronchi.

Albuterol (Ventolin, Proventil) -- Use for

bronchospasms refractory to epinephrine.
Relaxes bronchial smooth muscles by
action on beta-2 receptors, with little
effect on cardiac muscle contractility.
Drug Name First DOC because it can quickly reverse
asthma bronchoconstriction. Available
inhaled via MDI or HHN and orally for
those too young to use nebulizer.
Reserve oral dosing for preventative or
longer-acting use.
PO: 2-4 mg PO tid/qid; not to exceed 32
mg/d
Inhaler: 1-2 puffs q4-6h; not to exceed 12
puffs/d
Adult Dose
Nebulizer: Dilute 0.5 mL (2.5 mg) of 0.5%
inhalation solution in 1-2.5 mL of NS;
administer 2.5-5 mg q4-6h, diluted in 2-5
mL sterile saline or water
Pediatric Dose PO
2-5 years: 0.1-0.2 mg/kg tid; not to
exceed 12 mg/d
5-12 years: 2 mg tid/qid; not to exceed 24
mg/d
>12 years: Administer as in adults
Inhaler
<12 years: 1-2 puffs qid with tube spacer
 >12 years: Administer as in adults
Nebulizer
<5 years: Dilute 0.25-0.5 mL (1.25-2.5
mg) of 0.5% inhalation solution in 1-2.5
mL NS and administer q4-6h in equally
divided doses
>5 years: Administer as in adults
Contraindications Documented hypersensitivity
Beta-adrenergic blockers antagonize
effects; inhaled ipratropium may increase
duration of bronchodilatation;
Interactions
cardiovascular effects may increase with
MAOIs, inhaled anesthetics, TCAs, and
sympathomimetic agents
C - Safety for use during pregnancy has
Pregnancy
not been established.
Caution in hyperthyroidism, diabetes
mellitus, and cardiovascular disorders
Adverse effects include irritability,
particularly in children; tachycardia
(patients with baseline cardiac
abnormalities have decreased threshold
for tachyarrhythmia); and electrolyte
abnormalities (eg, hypokalemia)
Precautions Ventilation of areas that are not well
perfused may lead to ventilation-
perfusion mismatch, which can be
problematic in severe asthma
In outpatient setting, inappropriate use
(ie, overuse of MDIs) can lead to
paradoxical response of increased
bronchial obstruction and may induce
status asthmaticus
Levalbuterol (Xopenex) -- Moderately
selective beta2-receptor agonist. Active
enantiomer of racemic albuterol and more
potent than racemic mixture. Decreased
occurrence of adverse effects may allow
Drug Name
use of more frequent nebulizer therapy in
patients with acute asthma with less
concern over adverse effects of other
bronchodilators (eg, albuterol,
metaproterenol).
Adult Dose 0.63-1.25 mg nebulized q6-8h; may be
 given more frequently during emergent
situations
>12 years: Administer as in adults
<12 years: Not established; however, if
Pediatric Dose patient is albuterol intolerant and benefit
outweighs risk, 0.63 mg may be used q6-
8h
Contraindications Documented hypersensitivity
Beta-adrenergic blockers antagonize
effects; inhaled ipratropium may increase
duration of bronchodilatation;
Interactions
cardiovascular effects may increase with
MAOIs, inhaled anesthetics, TCAs, and
sympathomimetic agents
C - Safety for use during pregnancy has
Pregnancy
not been established.
Caution in hyperthyroidism, diabetes
mellitus, and cardiovascular disorders
Adverse effects include irritability,
particularly in children; tachycardia
(patients with baseline cardiac
abnormalities have decreased threshold
for tachyarrhythmia); and electrolyte
abnormalities (eg, hypokalemia)
Precautions Ventilation of areas that are not well
perfused may lead to ventilation-
perfusion mismatch, which can be
problematic in severe asthma
In the outpatient setting, inappropriate
use (ie, overuse of MDIs) can lead to
paradoxical response of increased
bronchial obstruction and may induce
status asthmaticus

Drug Category: Mast cell stabilizers

Cromolyn (Intal) -- Inhibits degranulation

Drug Name of sensitized mast cells following their
exposure to specific antigens.
Adult Dose Powder in caps for use with Spinhaler: 20
mg inhaled qid at regular intervals
MDI: 2 puffs (800 mcg/puff) qid at regular
intervals
Nebulizer: 20 mg inhaled qid at regular
 intervals
Once patient is stabilized, use lowest
effective dose
Powder in caps for use with Spinhaler
>5 years: 20 mg inhaled qid at regular
intervals
MDI
<5 years: Not recommended
>5 years: 2 puffs (800 mcg/puff) qid at
Pediatric Dose regular intervals
Nebulizer
2-12 years: 20 mg inhaled qid at regular
intervals
>12 years: Administer as in adults
Once patient is stabilized, use lowest
effective dose
Documented hypersensitivity; severe
Contraindications
renal or hepatic impairment
Interactions None reported
C - Safety for use during pregnancy has
Pregnancy
not been established.
Do not use with severe renal or hepatic
impairment; exercise caution when
Precautions
withdrawing drug because symptoms
may recur

Drug Category: Corticosteroids -- Maintenance medications that decrease

inflammatory mediators to limit airway remodeling. Must be taken regularly to be
beneficial. Glucocorticoids do not relieve acute bronchospasm, and short-acting
bronchodilators must be available. Multiple formulations are available that are not
equivalent on a per-dose or per-mcg basis. Inhaled corticosteroids are one of the
most important developments in asthma management because they decrease
inflammation. These agents are proven to improve lung function (FEV1 and
airway hyperactivity) and decrease symptoms, exacerbation frequency, and the
need for rescue inhalers.

Methylprednisolone (Solu-Medrol) -- For

treatment of inflammatory and allergic
reactions. By reversing increased
Drug Name capillary permeability and suppressing
PMN activity, may decrease
inflammation. Other corticosteroids may
be used in equivalent dosages.
Adult Dose Loading dose: 125-250 mg IV
 Maintenance dose: 4 mg/kg/d IV in
divided doses q4-6h
Loading dose: 2 mg/kg IV
Pediatric Dose Maintenance dose: 4 mg/kg/d IV in
divided doses q6h
Documented hypersensitivity; viral,
Contraindications
fungal, or tubercular skin infections
Coadministration with digoxin may
increase digitalis toxicity secondary to
hypokalemia; estrogens may increase
Interactions levels; phenobarbital, phenytoin, and
rifampin may decrease levels (adjust
dose); monitor patients for hypokalemia
when taking concurrently with diuretics
C - Safety for use during pregnancy has
Pregnancy
not been established.
Hyperglycemia, edema, osteonecrosis,
peptic ulcer disease, hypokalemia,
osteoporosis, euphoria, psychosis,
Precautions
growth suppression, myopathy, and
infections are possible complications of
glucocorticoid use

Drug Category: Bronchodilators -- Act to decrease muscle tone in both small

and large airways in lungs, thereby increasing ventilation.

Theophylline (Aminophyllin) -- Potentiates exogenous

catecholamines and stimulates endogenous catecholamine
Drug Name release and diaphragmatic muscular relaxation, which, in
turn, stimulates bronchodilation. For bronchodilation, near
toxic (>20 mg/dL) levels are usually required.
5.6 mg/kg loading dose (based on aminophylline) IV over 20
Adult Dose
min, followed by maintenance infusion of 0.1-1.1 mg/kg/h
6 weeks to 6 months: 0.5 mg/kg/h loading dose IV in first 12
h (based on aminophylline), followed by maintenance
infusion of 12 mg/kg/d thereafter; may administer
continuous infusion by dividing total daily dose by 24 h
Pediatric Dose
6 months to 1 year: 0.6-0.7 mg/kg/h IV in first 12 h as
loading dose, followed by maintenance infusion of 15
mg/kg/d; may administer as continuous infusion, as above
>1 year: Administer as in adults
Contraindications Documented hypersensitivity; uncontrolled arrhythmia,
peptic ulcers, hyperthyroidism, uncontrolled seizure
 disorders
Aminoglutethimide, barbiturates, carbamazepine,
ketoconazole, loop diuretics, charcoal, hydantoins,
phenobarbital, phenytoin, rifampin, isoniazid, and
sympathomimetics may decrease effects; allopurinol, beta-
Interactions
blockers, ciprofloxacin, corticosteroids, disulfiram,
quinolones, thyroid hormones, ephedrine, carbamazepine,
cimetidine, erythromycin, macrolides, propranolol, and
interferon may increase effects
C - Safety for use during pregnancy has not been
Pregnancy
established.
Caution in peptic ulcer, hypertension, tachyarrhythmia,
hyperthyroidism, and compromised cardiac function; do not
Precautions inject IV solution faster than 25 mg/min; patients diagnosed
with pulmonary edema or liver dysfunction are at greater
risk of toxicity because of reduced drug clearance

Drug Category: Anticholinergics -- Thought to work centrally by suppressing

conduction in vestibular cerebellar pathways. May have inhibitory effect on
parasympathetic nervous system.

Ipratropium bromide (Atrovent) -- Synthetic ammonium

compound very structurally similar to atropine. May provide
additive benefit to inhaled beta-2 agonists when treating
severe acute asthma exacerbations. Also may be
Drug Name
alternative bronchodilator for patients unable to tolerate
inhaled beta-2 agonists. Children may be more responsive
to parasympathetic inhibition than adults because children
appear to have more cholinergic receptors.
MDI: 2 puffs (18 mcg/puff) qid
Adult Dose
Nebulizer: 500 mcg tid/qid
MDI
3-14 years: 1-2 puffs (18 mcg/puff) tid/qid
>14 years: Administer as in adults
Nebulizer
Pediatric Dose <3 years and neonates: 25 mcg/kg/dose tid
<14 years: 125-250 mcg tid/qid
>14 years: Administer as in adults
Very effective in children and usually given combined with
beta-agonists
Contraindications Documented hypersensitivity
Drugs with anticholinergic properties (eg, dronabinol) may
Interactions
increase toxicity; albuterol may increase effects
Pregnancy B - Usually safe but benefits must outweigh the risks.
Not indicated for emergent episodes of bronchospasm;
Precautions caution in narrow-angle glaucoma, prostatic hypertrophy,
and bladder neck obstruction
FOLLOW-UP Section 8 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Further Inpatient Care:

• Sedatives

o Patients may benefit from sedatives in very small doses and under
controlled, monitored settings. Sedatives should be used
judiciously, if at all. For example, lorazepam (0.5 or 1 mg
intravenously) could be used for patients who are very anxious and
are undergoing appropriate and aggressive bronchodilator therapy.

o More powerful agents (eg, oxybutynin) can be administered to

intubated patients to achieve sedative, amnestic, and anxiolytic
effects.

• Mechanical ventilation

o Consider mechanical ventilation as a last resort in patients with

status asthmaticus.
o Mechanical ventilation in patients with asthma requires careful
monitoring because these patients have high end-expiratory
pressure and, therefore, are at very high risk for pneumothorax.
o Mechanical ventilation, when used in patients with asthma, is
usually required for less than 72 hours; however, in occasional
patients with severe bronchospasm, mechanical ventilation can be
prolonged. In these situations, consultation with a pulmonologist or
another expert in mechanical ventilatory techniques is likely useful.

• Other treatments

o Other treatments have been used, but none is well proven in

patients with severe acute asthma.
o A combination of helium and oxygen known as heliox (ie, 30/70
mixture) has been used, but this treatment should only be
considered in patients who are able to take deep breaths because
the treatment is dependent on inspiratory flow.
o Intravenous magnesium sulfate can be tried, especially in pregnant
women, as an adjunct to beta-2 bronchodilator therapy.
 o Nitrate oxide has recently been tried in a child with refractory
asthma. The future role of this therapy remains to be determined.
o Leukotriene modifiers are useful for treating chronic asthma but not
acute asthma. This treatment may be beneficial if used via a
nebulizer, but it remains experimental.

• Hydration
o Hydration, such as normal saline at a reasonable rate (eg, 150
mL/h), is essential.
o Special attention to the patient's electrolyte status is important.
o Hypokalemia may result from either steroid use or beta-agonist
use. Correcting hypokalemia helps wean an intubated patient with
asthma. Hypophosphatemia may result from poor oral intake and is
also an important consideration when weaning such patients.

• Intravenous antibiotics
o Intravenous antibiotics are important in patients with acute asthma
only if they have evidence of an infection (eg, pneumonia, sinusitis).
o In some situations, sinus imaging using CT scanning or plain
radiography may be essential to help rule out chronic sinusitis.

Further Outpatient Care:

• Instruct patients to use of inhalers appropriately, to be compliant with

therapy, and to practice stress-avoidance measures. Stress factors (ie,
triggers of asthma attacks) include pet dander, house dust, and mold.
Strongly discourage patients from smoking; this practice should be
avoided at all costs. Finally, appropriate follow-up is important, as is
checking the patient's peak flow meter and FEV 1 at home or in the office,
respectively.

• Children with asthma commonly present with normal FEV1, and,

accordingly, more sensitive lung function testing should be undertaken
with regular IOS assessments. Medication titration may be usefully guided
by IOS resistance and reactance values.

Deterrence/Prevention:

• Status asthmaticus can be prevented if patients are compliant with their

medications and they avoid stress factors; however, it can occur even
when patients are compliant and doing well as outpatients. In such
situations, search for an occult infection (eg, RSV in children but rarely in
adults; occult sinus infection).

• Prevention of status asthmaticus may be aided by monitoring forced

oscillation test results rather than spirometry findings. This is particularly
 true for children younger than 12 years; however, adults with reactive
airways may be undertreated if the criterion for stability and normality is a
spirometric FEV1 greater than 80% of the predicted value.

Complications:

• Pneumothorax may complicate acute asthma, either because of increased

airway pressure or as a result of mechanical ventilation. Superimposed
infection can also occur in intubated patients. Patients may require a chest
tube for pneumothorax or aggressive antibiotic therapy for a
superimposed infection.

Prognosis:

• In general, unless a complicating illness such as congestive heart failure

or chronic obstructive pulmonary disease is present, with appropriate
therapy status asthmaticus has a good prognosis. A delay in initiating
treatment is probably the worst prognostic factor. Delays can result from
poor access to health care on the part of the patient or even delays in
using steroids. Patients with acute asthma should use steroids early and
aggressively.

Patient Education:

• One important aspect of patient education is that asthma is a disease of

airway inflammation; it is not simply bronchospasms. Airway inflammation
is a continuing process that renders patients with asthma vulnerable to
acute bronchospasms. Symptoms are more dependent on
bronchospasms than on inflammation; thus, symptoms may become
minimal in the presence of continued peripheral airway inflammation.
Because patients often wish to discontinue inhaled corticosteroids when
they are free of acute bouts of wheezing, educating them regarding the
need for controller medications to minimize peripheral airway inflammation
is important.

• Patients can be shown the results of forced oscillation testing that occur
with peripheral airway inflammation and obstruction. Review the test
results with patients and show them the improvement with inhaled
corticosteroids and the deterioration when they are not compliant with anti-
inflammatory medications. This information may materially enhance
patients' awareness of the need for continuing treatment, despite an
absence of wheezing.

• For excellent patient education resources, visit eMedicine's Asthma

Center. Also, see eMedicine's patient education articles, Asthma, Asthma
FAQs, and Understanding Asthma Medications.
 MISCELLANEOUS Section 9 of 10
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Medical/Legal Pitfalls:

• Failure to initiate steroid therapy or intubation with mechanical ventilation

• Failure to obtain sinus imaging or to monitor the patient's electrolyte

balance

• Failure to admit a wheezing patient with a normal PCO2: Such patients

typically have respiratory muscle fatigue and require hospital admission.

• Failure to treat expediently, especially with bronchodilators

• Failure to educate patients upon discharge about the appropriate use of

their inhalers, the importance of therapy compliance, and the efficacy of
stress-avoidance measures

Special Concerns:

• Treat pregnant women with acute asthma in the same aggressive manner
as nonpregnant women. Respiratory acidosis can be detrimental to both
the fetus and the mother. Use special abdominal shielding during chest
radiography or sinus imaging.

• Treat children with acute asthma in manner similar to that for adults,
except when children are mechanically ventilated, because their chests
are more compliant and require special attention.

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